Abiotic and biotic factors affecting the immune system of aquatic species: A review

Highlights

• •Abiotic environmental factors, including temperature, salinity, pH, hypoxia, and pollutants, significantly influence immune functions in aquatic animals.
• •Pathogenic and parasitic infections, as biotic stressors, markedly inhibit both innate and adaptive immune responses, thereby heightening susceptibility to disease.
• •Aquatic species' immune systems demonstrate structural and functional diversity, influenced by evolutionary adaptations to specific ecological niches.
• •Integrating environmental and immunological knowledge is essential for enhancing aquaculture resilience, disease management, and the sustainability of aquatic ecosystem health.

Abstract

The immune response of aquatic organisms is affected by biotic and abiotic elements, determining their health and survival. Thus, this review aimed to integrate existing research on how environmental factors (temperature, salinity, pH, pollution) and biotic factors (infections, parasites, and the microbiome) shape immune function in aquatic animals. Aquatic animals, which include fish, crustaceans, and molluscs, have innate and adaptive immune systems that are predominant in non-mammalian species. Abiotic stresses such as temperature variations and pollution can compromise immune responses, putting them at higher risk of infection. Biotic interactions also influence immunological responses, resulting in immunosuppression under elevated pathogen burden and interspecies competition. Therefore, understanding these aspects in aquaculture, ecosystem management, and conservation initiatives can offer insights into the impact of environmental changes and stresses on the immunological resilience of aquatic animals.

Introduction

The immune response of aquatic organisms is a complex and dynamic mechanism essential for their survival and overall health, affected by various biotic and abiotic variables. Biotic factors comprise interactions with diseases, parasites, and competitors, whereas abiotic factors involve environmental variables such as temperature, salinity, pH, and pollutant presence [1]. Understanding the influence of these elements on immune responses is crucial for managing aquatic ecosystems, enhancing aquaculture methods, and evaluating environmental health. Fish, crustaceans, molluscs, and amphibians exhibit various immunological responses tailored to their distinct environments and behaviours, which can be classified into innate and adaptive immunity [[2], [3], [4]]. Innate immunity is the primary defence mechanism that offers rapid, non-specific protection against infections. Meanwhile, adaptive immunity is a more targeted and enduring response to protect against previously encountered infections, often observed in teleost fish and certain amphibians.

Pathogen load and interspecies interactions are biotic factors that affect the immune response of aquatic organisms [[5], [6], [7], [8], [9], [10], [11]]. High pathogen densities suppress their immune responses, making these animals vulnerable to infections [12]. Additionally, competing for resources may induce stress in aquatic species, potentially compromising their immunological systems [13]. Abiotic variables such as excessive temperatures, salinity variations, and pollution can also impair immune processes, increasing the species’ susceptibility to illnesses [[14], [15], [16]]. Exposure to heavy metals and endocrine-disrupting chemicals has been demonstrated to hamper immune system efficacy in numerous aquatic species [17].

In this review, the literature on the interaction between biotic and abiotic stimuli and the immune systems of aquatic organisms was synthesised to highlight their significant influence on immune responses. In addition, this review elucidated the interactions of these variables that affect health outcomes in aquatic ecosystems and aquaculture, offering insights for the stakeholders to improve the health of aquatic species and the sustainability of aquatic resources.

Overview of immune systems in aquatic animals

The immune system, namely innate (non-specific) and adaptive (specific) immunity, is critical in fighting infections in aquatic animals [[18], [19], [20]]. The two systems function together to preserve the organism despite significant variances in their approaches and prevalence among species (Fig. 1). Innate immunity is more pivotal for non-mammals, such as aquatic animals, while adaptive immunity may be rudimentary or non-existent, depending on the species. Innate immunity serves as the primary defence mechanism in all animals, including aquatic species [21]. It is non-specific and targets a wide array of pathogens without the need for prior exposure. Furthermore, innate immune responses are instantaneous and involve a variety of cellular and humoral elements.

Fig. 1.

Immune systems in aquatic animals.

Aquatic animals display a notable diversity in the structures and functions of their immune systems. All aquatic animals exhibit innate immunity as a non-specific initial defence mechanism; however, the presence and complexity of adaptive immunity differ among species. Jawed fish are an example of vertebrates that exhibit advanced adaptive immune systems, characterised by specific immune responses and the capacity for immunological memory [[22], [23], [24]]. In contrast, invertebrates depend solely on innate immunity, employing diverse cellular and humoral components to identify and eradicate pathogens. Several aquatic invertebrates do not possess an adaptive immune system, depending solely on their innate immune defences for protection against infections [25]. The innate immune systems in molluscs, echinoderms, and crustaceans are well-developed to compensate for the lack of adaptive immunity. This immunological diversity in aquatic animals illustrates their evolutionary adaptations to distinct environments, with the immune system being essential for health and survival.

According to Guryanova and Ovchinnikova [26], innate immunity consists of several immune cells responsible for recognising, phagocytosing, and combating pathogens. Phagocytosis is a process in which cells consume and digest pathogens and is part of an animal’s primary defence mechanism. Phagocytic cells, such as macrophages and neutrophils, are the primary effectors of the innate immune systems in fish and other aquatic vertebrates [27,28]. Macrophages serve as the initial defence against pathogens and regulate the inflammatory responses. Meanwhile, natural killer (NK) cells, found in most vertebrates, including fish, identify and eliminate diseased or abnormal cells [29]. These cells do not require antigen recognition to operate, enabling them to function swiftly against infections. Hemocytes are essential in the immune response of aquatic invertebrates, including molluscs and crustaceans. These immune cells are crucial for organisms that lack an adaptive immune response and must depend only on innate defences. Hematocytes exert their protective functions through phagocytosis, encapsulation, and the synthesis of antimicrobial compounds [30,31].

Apart from cellular responses, aquatic animals have humoral components for immune protection in the form of soluble molecules in the blood or body fluids. The humoral factors include lysozyme, an enzyme present in the blood, tissues, and mucus of fish and invertebrates, crucial for fighting bacterial infections [[32], [33], [34]]. This enzyme degrades the peptidoglycan layer in bacterial cell walls, resulting in bacterial cell death [33]. The complement system is another component of the innate immune response in fish and other aquatic vertebrates, which functions similarly to that in mammals to recognise and clear pathogens. This system consists of a cascade of proteins that mark pathogens to facilitate their elimination through cell lysis and enhance inflammation [35]. Antimicrobial peptides (AMPs) are small molecules that demonstrate broad-spectrum activity against bacteria, viruses, and fungi [[36], [37], [38]]. These peptides are present in the mucus, blood, and tissues of various aquatic species, such as fish and amphibians. Defensins and hepcidins are examples of AMPs in aquatic vertebrates for a swift and efficient defence against microbial invasions [39]. Furthermore, carbohydrate-binding proteins, such as lectins, are essential in invertebrates and lower vertebrates for pathogen recognition and clearance. This peptide aids in pathogen elimination by recognising its surface carbohydrates [40,41].

Adaptive immunity is more advanced in vertebrates such as fish due to its specificity to antigens and the ability to form immunological memory [42], allowing the animal to respond more efficiently to future encounters with identical pathogens [43]. It depends on the function of lymphocytes, specifically B cells and T cells, and the synthesis of antibodies. Adaptive immunity is well developed in jawed vertebrates, including bony fish (teleosts) and cartilaginous fish (sharks and rays). Teleost fish possess a functional adaptive immune system similar to mammals but with distinct characteristics. In contrast, Jawless vertebrates, including lampreys and hagfish, have adaptive immune system that operates independently of immunoglobulins. These species utilise lymphocyte receptors (VLRs) for the recognition and response to pathogens [44]. The VLRs are structurally different from antibodies while fulfilling a comparable role in antigen recognition [45]. This system exemplifies the diversity of immune strategies present in vertebrates.

Nutritional immunity is defined as the host's active sequestration of essential trace metals to inhibit pathogen growth during infection [[46], [47], [48], [49], [50]]. Nutritional immunity serves as a crucial adaptive mechanism in aquatic ecosystems, linking environmental factors such as salinity, temperature, pollution, and pH with immune responses, all of which influence water chemistry and metal bioavailability. Aquatic vertebrates, including fish, employ iron-binding proteins such as transferrin and hepcidin to diminish extracellular iron availability during infections [51,52]. This mechanism deprives pathogens of an essential resource while also regulating systemic iron levels. The expression of hepcidin is modulated by inflammatory signals and environmental stressors, highlighting its dual role in immunity and metal homeostasis [53]. Additionally, certain pathogens in aquatic environments have developed siderophore-mediated strategies to extract iron from the host or surroundings, underscoring the evolutionary conflict between host defences and microbial acquisition methods [54]. The results of this competition are frequently influenced by the availability of abiotic nutrients in the water column or sediment, positioning nutritional immunity as both an internal immune strategy and a response that is sensitive to external environmental conditions. Nutritional immunity acts as a functional connection between abiotic stressors, such as nutrient limitation and water chemistry, and biotic challenges, including infections. This illustrates the evolutionary adaptations of aquatic species in defending themselves through the regulation of metabolic resources in varied and dynamic environments.

Biotic factors influencing immune responses

Biotic variables influence immunological responses in fish. Thus, it is crucial to understand how fish protect themselves from illnesses and other risk factors in the wild and farmed environments. The biotic variables influencing immune responses in aquatic organisms include pathogens (bacteria, viruses, fungi), parasites (protozoans and helminths), and the internal microbiome.

Pathogens

Pathogens, including bacteria, viruses, and fungi, represent a major biotic stressor to fish's immune system (Table 1). Pathogenic threats compromise the immune system and increase the fish’s susceptibility to infections, which may result in significant mortality and economic losses in aquaculture [55]. Aquatic animals depend significantly on their innate immune systems to combat bacterial infections [56]. According to Wangkahart et al. [57], the innate immune system identifies bacterial components, including lipopolysaccharides (LPS) and flagellin, to initiate an immune response. Some bacteria, such as Vibrio spp., Aeromonas spp., and Edwardsiella spp., can evade or suppress host immune responses to facilitate their survival within the host. These microbes secrete toxins that harm immune cells or inhibit phagocytosis. Pathogens can also affect the fish’s adaptive immune response by disrupting antibody production responsible for neutralising bacterial toxins, leading to chronic infections that are more difficult to manage and treat [[58], [59], [60]]. Therefore, understanding the influence of pathogens on immune responses in aquatic animals is essential for managing fish health in aquaculture, improving infection resilience, and conserving wild populations.

Table 1.

Pathogen effects on the immune system of aquatic species.

Pathogen	Aquatic species	Effects on the immune system	References
Aeromonas veronii	Freshwater fish	Immunosuppression and acute infections in aquatic animals decrease mucosal defences	De Silva and Heo [61]
Microsporidia	Fish (general)	Induces immunosuppression in aquatic animals, impacting specific and non-specific immune defences	Bojko and Stentiford [62]
Ichthyophthirius multifiliis	Freshwater fish (tilapia, catfish, carp)	Reduced immune reaction and caused skin sores on fish	Teixeira Alves and Taylor [63]
Probiotic bacteria	Shrimp, fish (general)	Improved non-specific defences and bacterial resistance in aquaculture species	Jamal et al. [64]
Vibriosis	Marine fish	Impacted innate defences and compromised the immune system, resulting in elevated mortality rates among aquaculture species	Ina-Salwany et al. [65]
Vibrio vulnificus	Marine fish, shellfish	Induced immunosuppression and tissue necrosis, compromising the immune system in marine organisms	Allam and Raftos [66]
Listeria monocytogenes	Fish (general)	Disruption of the mucosal barriers affected the fish's immune system, reducing its innate defence	Morley [67]
Spring viremia of carp virus (SVCV)	Cyprinus carpio (Common carp)	Infects carp species by suppressing their innate and adaptive immune responses	Morley [67]
Saprolegnia spp.	Freshwater fish (salmon, trout, catfish)	Affected immune responses through tissue damage and the suppression of protective barriers in aquatic organisms	Duan et al. [68]
Aeromonas salmonicida	Salmonids (salmon, trout)	Impaired immune responses in salmonids led to significant tissue necrosis and impaired specific and nonspecific immunity	Rauta et al. [59]
Aeromonas hydrophila	Freshwater fish (carp, catfish, tilapia)	Inhibited innate immune responses and diminished the host's defence mechanisms	Ben Hamed et al. [69]
Flavobacterium columnare	Freshwater fish (tilapia, catfish, carp)	Infected multiple fish species, compromising their immune defences and causing skin lesions that further diminish immune responses	Teixeira Alves and Taylor [63]
Edwardsiella tarda	Eels, catfish, and other freshwater fish	Impaired immune responses in eels hindered the production of immune cells and elevated their vulnerability to bacterial infections	Shoemaker et al. [70]
Vibrio spp.	Marine fish and shellfish	Immunosuppression in fish and shellfish weakened their immune responses and increased susceptibility to diseases	Derome et al. [71]
Yersinia ruckeri	Salmonids (salmon, trout)	Redmouth disease in fish impaired immune responses and heightened vulnerability to secondary infections	Mydlarz et al. [72]
Aeromonas hydrophila	Zebrafish (Danio rerio)	The bacterial infection induces a pro-inflammatory response, increases oxidative stress, and results in tissue damage in essential organs such as the kidney. This immune activation constitutes a component of the fish's defense mechanism against bacterial infection.	Rodríguez et al. [73]
A. hydrophila, A. salmonicida, L. garvieae, S. agalactiae, and V. parahaemolyticus	Goldfish (Carassius auratus)	The pathogens (A. hydrophila, A. salmonicida, L. garvieae, S. agalactiae, and V. parahaemolyticus) adversely impact the immune system, as these bacteria are recognized for inducing illnesses in fish.	Yi et al. [74]
Aphanomyces invadans	Cirrhina mrigala	Aphanomyces invadans compromises the immune system by inducing infections that elevate mortality rates in untreated fish.	Harikrishnan et al. [75]
Aphanomyces invadans	Zebrafish (Danio rerio)	Aphanomyces invadans compromises the immune system by inducing infections that elevate mortality rates in untreated fish.	Yang et al. [76]
species of Vibrio	Wild eel	Vibrio species influence the immune system of wild eels by colonizing and potentially compromising the mucosal barrier, which serves as the primary defense mechanism in fish immunity.	Carda-Diéguez et al. [77]
Vibrio spp., Aeromonas hydrophila, Edwardsiella tarda	Orange-spotted grouper (Epinephelus coioides)	The pathogens may impair the immune system by inducing infections that result in tissue damage and systemic disease.	Kuo et al. [78]

Bacterial pathogens

Bacterial infections are prevalent in freshwater and marine fish, particularly in aquaculture settings, due to the high fish density [79]. Therefore, it is important to manage bacterial diseases to prevent morbidity and mortality and maintain fish health. Vibrio spp., for instance, is responsible for a significant disease affecting marine fish and shrimp known as vibriosis. As a result, numerous studies have investigated the effects of Vibrio spp. on infections, immune modulation, and preventive strategies across various fish species [[65], [80], [81], [82], [83], [84], [85], [86], [87]]. It was found that these bacteria triggered immune responses by activating the innate immune system to produce antimicrobial peptides (AMPs) and activate phagocytic cells. Moreover, Vibrio infections upregulated immune-related genes in fish, such as the cytokine IL-1β, which is crucial for inflammation and immune cell recruitment [88].

Aeromonas spp., particularly Aeromonas hydrophila, is recognised for its substantial impact on the immunological response of numerous fish species. The pathogen infiltrates the host by disrupting the integumentary or gastrointestinal barriers, regulating cytokines and triggering inflammation. In Zhejiang province, China, A. hydrophila outbreaks caused substantial economic losses by inducing biofilm formation and mass mortalities in aquaculture species [89,90]. Aeromonas spp. regulated the immunological response of fish via many pathways, affected by bacterial virulence mechanisms and extrinsic factors such as nutrition and environmental conditions. In red crucian carp, A. hydrophila infection affects the gut-liver axis, modifying immune signalling pathways that regulate pro- and anti-inflammatory cytokines [89]. Recent research indicated that the removal of virulence factors, such as orf02889 from A. hydrophila, increased the expression of crucial immune-related genes in zebrafish, including interleukin-1β (il-1β) and antibacterial peptides such as lysozyme (lyz-c). These changes suggest the immune response may be activated under specific conditions, potentially facilitating vaccine development [90]. Nutritional therapies such as food supplementation with immunostimulants have also shown promising results in managing infections in aquaculture species. For example, administering algal extracts to Labeo rohita (rohu) enhanced their resistance to A. hydrophila due to increased neutrophil and lysozyme activities. Furthermore, the algal diet improved their survival rates compared to the control group after bacterial challenge [91]. This finding illustrates that dietary and environmental variables can influence the fish’s immune response to Aeromonas infections.

Edwardsiella tarda significantly influences aquatic animals' immune responses by activating innate and adaptive defences while employing evasion mechanisms that facilitate its persistence and pathogenicity. Comprehending these immune interactions is essential for formulating effective vaccines and treatment strategies to safeguard aquatic species, especially in aquaculture settings where E. tarda represents a considerable risk. Edwardsiella tarda is another pathogenic bacterium that significantly affects the immune response of aquatic animals [92,93]. When exposed to E. tarda infection, aquatic animals initiate an oxidative burst that produces reactive oxygen species (ROS) to eliminate pathogens [94,95]. However, E. tarda can neutralise reactive oxygen species (ROS) and continue to evade the host's immune mechanisms by producing antioxidant enzymes, such as iron-cofactored superoxide dismutase (FeSOD) [96,97]. Meanwhile, infected zebrafish and flounder generated pro-inflammatory cytokines to attract immune cells to the infection site as a strategy against E. tarda attacks. Nonetheless, E. tarda has developed mechanisms to evade detection and partially circumvent the immune response [98], such as inhibiting macrophage activity and reducing phagocytosis to reduce the innate immune response [99].

The adaptive immune response, which encompasses humoral and cell-mediated immunity, is essential for defence against E. tarda [100]. Infected flounder and tilapia were found to increase their antibody production, particularly IgM, to neutralise E. tarda [101]. Meanwhile, cellular immunity in aquaculture species helps protect them against this bacterium by activating T-cells and other immune cells to eradicate infected cells. Vaccinating flounder and carp with inactivated E. tarda has been proven to increase antibody production and cellular immune responses [102,103], serving as critical measures for safeguarding aquatic species against E. tarda infections [102]. Aquatic species infected with E. tarda also demonstrated notable metabolic and transcriptomic alterations. For instance, exposure to E. tarda triggered metabolic changes in Chinese soft-shelled turtles that enhanced their immune functions by elevating energy and protein metabolism [104]. Transcriptomic analyses in flounder and tilapia exhibited the upregulation of immune-related genes associated with inflammation and pathogen recognition as a response to E. tarda infection [105].

Synergistic effects of temperature and bacterial infection

The interaction between abiotic and biotic stressors significantly influences immune responses in aquatic species. Temperature fluctuations can exacerbate bacterial infections, leading to a synergistic effect that undermines host immunity [[49], [106]]. Increased water temperatures frequently enhance pathogen virulence, growth rates, and transmission dynamics, while concurrently compromising the host's immune function [107]. Vibrio spp. and Aeromonas hydrophila demonstrate increased proliferation in warmer conditions, leading to more severe infections and immune suppression in fish species, including Nile tilapia and common carp [108].

High temperatures induce oxidative stress and immune dysregulation in aquatic animals, weakening essential immune components, including phagocytic activity, lysozyme levels, and cytokine signalling [109,110]. The modifications diminish the host's ability to effectively eliminate pathogens. The molecular synergy is evident, as temperature stress influences the expression of immune genes such as IL-1β, TNF-α, and heat shock proteins, which collectively modulate responses to bacterial challenges [111]. The compounding effect is notably significant in aquaculture, where temperature regulation is essential for controlling disease outbreaks. Recognizing and managing the synergistic impacts of thermal and bacterial stressors is essential for sustaining immune resilience in aquatic organisms, especially in the context of global warming and intensified aquaculture practices.

Virus

Viral infections pose significant challenges in aquaculture due to their high transmissibility and the complexities associated with treating viral diseases after they are transmitted [112]. Numerous viruses directly inhibit or circumvent the immune system, facilitating their rapid replication within host cells. Infectious hematopoietic necrosis virus (IHNV) is a major viral pathogen that predominantly impacts salmonid fish species, especially in freshwater ecosystems [[113], [114], [115]]. The immune response involves the activation of interferons, signalling proteins that impede viral replication. Chaves-Pozo et al. [116] demonstrated that interferon-stimulated genes (ISGs) are essential for fish protection against IHNV, as they enhance the antiviral state of the immune cells. Viral hemorrhagic septicemia virus (VHSV) is a viral pathogen that impacts various fish species, resulting in internal haemorrhaging. Fish activate innate immune responses via the secretion of cytokines such as TNF-α and IFN-γ. Infected fish display a robust antiviral response alongside suppression of adaptive immunity against VHSV, highlighting the virus's capacity to circumvent more specific immune defences [117].

Aquaculture increasingly use antiviral agents to manage viral outbreaks that threaten fish and shellfish populations. Antiviral drug development for aquaculture remains in its early stages; however, several promising examples demonstrate the potential effectiveness of this therapy in managing viral infections. Mondal et al. [118] revealed the application of polyvinylpyrrolidone-iodine (PVP-I) serves as an example of a broad-spectrum antiseptic utilized to inhibit viral replication and decrease viral loads in aquaculture systems. PVP-I effectively inhibits IHNV in salmonids by preventing viral adhesion to epithelial cells, thereby restricting infection spread. Another example involves the utilization of coumarin derivatives, which exhibit antiviral properties against IHNV. Research indicates that coumarin compounds can inhibit viral entry and replication, resulting in a reduced mortality rate among infected fish populations [114]. Antiviral activities against the spring viraemia of carp virus have been identified in extracts of medicinal plants such as Schisandra chinensis, thereby confirming their potential application as natural antivirals in aquaculture [119]. The general application of antiviral drugs in aquaculture is limited by stringent regulatory approvals and the necessity for extensive field trials to demonstrate their efficacy and safety. The control of viral diseases in aquaculture relies significantly on biosecurity protocols, vaccination initiatives, and selective breeding for enhanced disease resistance.

Fungus

Fungal infections frequently take advantage of weakened immune systems or are promoted by environmental factors like inadequate water quality that support fungal proliferation., elevating mortality rates within affected populations [[120], [121], [122]]. Saprolegnia spp. is recognised as the most prevalent fungal infection, a water mould that induces saprolegniosis in freshwater fish or infections of the skin and gills [123]. The fish’s innate immune system prevents the spreading of infection by activating reactive oxygen species (ROS) and the release of pro-inflammatory cytokines. Parra-Laca et al. [124] demonstrated enhanced melanin production in fish during Saprolegnia infections to encapsulate and isolate the pathogen.

Scientists have developed and implemented various preventive measures to mitigate fungal infections in aquatic species, focusing on environmental management and direct interventions for fish health. Maintaining optimal water quality is essential, as suboptimal conditions promote fungal proliferation [123]. Regular monitoring and control of parameters, including temperature, pH, and dissolved oxygen levels, resulted in decreasing the growth of fungal. According to Hu et al. [125], hydrogen peroxide and potassium permanganate are significant antifungal agents employed in the management of Saprolegnia outbreaks in aquaculture. Additionally, significant research efforts are directed towards immunostimulants and probiotics that enhance the immune response to fungal infections. Barde et al. [126] indicate that biological interventions enhance innate immunity, thereby protecting fish from environmental stressors. Another promising strategy involves selective breeding for resistance to Saprolegnia infections. Research in genetics and breeding initiatives aims to create fish strains that exhibit improved resistance to fungal pathogens [127]. Vaccine development against Saprolegnia remains in the experimental phase and is being investigated as a potential long-term preventive measure [128].

The application of aquatic antifungal agents is governed by considerations of food safety, environmental sustainability, and the welfare of aquatic organisms. Various regulatory frameworks govern the approval, application, and monitoring of antifungal agents used in the aquaculture industry. Antifungal agents require rigorous evaluation by regulatory bodies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Rodgers and Furones [129] examine the safety, efficacy, and potential environmental impacts of the substances to reduce risks to consumers and ecosystems. Some antifungal agents, including malachite green, are restricted or prohibited because of their carcinogenic characteristics and detrimental environmental impacts [130,131]. Regulatory bodies determine allowable antifungal agents and set maximum residue limits (MRLs) for aquaculture products meant for human consumption [132]. According to Patil et al. [133], producers must comply with Good Aquaculture Practices (GAP), which focus on disease prevention and the judicious use of antifungal agents to mitigate the risk of drug resistance and environmental contamination.

Monitoring programs, such as the National Residue Program (NRP) in the United States, are essential and perform periodic assessments and residue testing to ensure compliance with established safety thresholds. These initiatives are essential for monitoring antifungal usage to ensure that aquaculture products adhere to acceptable safety limits [134]. Training and education programs enhance the appropriate use of antifungal agents, emphasizing correct dosages, withdrawal periods, and waste management to mitigate environmental discharge and protect aquatic ecosystems. Comprehensive regulatory measures will enable the aquaculture industry to sustainably manage fungal infections, reduce risks associated with antifungal agents, and ensure the production of safe, healthy aquatic products for global consumption. The integrated management strategies that combine water quality control, targeted antifungal treatments, genetic enhancement, and immunoprophylaxis effectively protect aquaculture from fungal infections, thereby ensuring healthier fish populations and enhancing sustainability within the industry.

Parasites

Parasites, such as protozoans and helminths, are notable biotic stressors in fish, often evading or manipulating the host immune system to establish chronic infections [135]. Protozoan parasites, including Ichthyophthirius multifiliis (Ich) and Cryptocaryon irritans, significantly impact aquaculture by affecting all aquatic species [136,137]. Ich is responsible for white spot disease in freshwater fish, inducing immune responses such as heightened mucus production to encapsulate the parasite and activate complement proteins to lyse its cells. In fish with adaptive immunity, their stress response to parasitic infection is characterised by the rise of antibody levels and heat shock proteins are upregulated [138]. Cryptocaryon irritans induce analogous infections in the gills and skin of marine fish, triggering a protective mechanism to thwart additional parasitic invasion known as gill hyperplasia [139]. Digenetic trematodes are multicellular parasitic helminths that complicate immune responses because of their intricate life cycles, frequently resulting in chronic infections. Wu et al. [102] reported that trematode infections in fish lead to granuloma formation, where immune cells encapsulate the parasites to isolate and neutralise them.

In summary, parasitic infections pose a major concern in aquaculture, as protozoans and helminths can evade or manipulate the immune system. Understanding the fish’s immune responses, including mucus production, expression of heat shock proteins, gill hyperplasia, and granuloma formation. Future studies should focus on developing effective treatments and preventive strategies to reduce the impact of parasitic diseases in aquaculture, such as vaccines and improved biosecurity measures.

Microbiome and symbiotic interactions

The fish microbiome is crucial for regulating immune responses and sustaining overall health [140]. Microbial communities act as a primary defence mechanism by inhibiting the colonisation of harmful pathogens through competitive exclusion and the synthesis of antimicrobial compounds (Zhang et al. [141]. Furthermore, the microbiome is crucial in maintaining immune homeostasis through its interactions with the host's immune system, affecting innate and adaptive immune responses. Beneficial bacteria in the gut, skin, and gills enhance immune function by strengthening physical barriers, including the mucosal layer, and facilitating the production of immune effectors [[142], [143], [144], [145]].

The microbiome significantly contributes to enhancing immune resilience in fish, primarily through its interactions with beneficial probiotic bacteria. These mechanisms are critical for managing fish health in aquaculture and facilitate the development of targeted probiotic therapies to enhance disease resistance in fish populations. Probiotics improve fish immunity in aquaculture, primarily influencing the mucosal immune system in the gastrointestinal tract [146]. These live beneficial bacteria regulate immune responses by stimulating IgM to neutralise pathogens and activate the complement system [147,148]. In addition, probiotics enhance AMP synthesis, which is the synthesis of small molecules that directly target and eliminate invading pathogens. Recent studies have reported that probiotic supplementation significantly promoted Toll-like receptor (TLRs) expression in fish [[149], [150], [151]]. These pattern-recognition receptors are crucial to the innate immune system, identifying pathogen-associated molecular patterns (PAMPs), including bacterial lipopolysaccharides and viral RNA. Upon recognition of these PAMPs, TLRs activate immune signalling pathways, resulting in downstream immune responses such as producing pro-inflammatory cytokines and recruiting immune cells to infection sites [152].

Abiotic factors affecting immune responses

Aquatic animals live in environments characterized by frequent fluctuations in physical and chemical conditions, which can substantially affect their immune responses. Factors including temperature, salinity, pH, oxygen levels, and pollutants significantly influence the function and efficacy of both innate and acquired immune systems. These stressors can either inhibit or stimulate immune pathways, influencing disease susceptibility, resistance, and overall health. Fig. 2 illustrates the primary abiotic factors and their impacts on the immune system components in aquatic species, facilitating a deeper understanding of these interactions.

Fig. 2.

Abiotic factors influencing immune systems in aquatic animals.

Temperature

Temperature is a vital abiotic factor that has substantial impacts on the innate and adaptive immune responses of aquatic animals. Aquatic animals are ectothermic and, thus, rely on external temperatures to regulate their physiological processes, such as immune function [153]. Water temperature fluctuation can either strengthen or diminish the fish’s immune responses, influencing their susceptibility to pathogens. As the primary defence mechanism, innate immunity is more sensitive to temperature variation. When the temperature decreases, immune cells' (macrophages and phagocytes) activities are reduced, thereby impairing their capacity to recognise and eliminate pathogens [154]. Furthermore, cold conditions lower enzymatic activities critical for immune defence, thus reducing the efficacy of lysozyme and complement proteins. Meanwhile, elevated temperatures can initially enhance immune function. However, prolonged exposure may lead to thermal stress, resulting in decreased immune efficiency and heightened disease risk.

Table 2 demonstrates that the adaptive immune responses and innate immunity of aquatic animals are influenced by temperature, particularly lymphocyte proliferation, antibody production, and expression of major histocompatibility complex (MHC) molecules [155,156]. Cold conditions frequently result in delayed immune responses, characterised by reduced antibody production and poorer capacity to fight infections [157]. In contrast, higher temperatures can accelerate immune responses. Nonetheless, the accuracy of immune recognition may be compromised under this condition, leading to decreased efficiency in pathogen clearance. Temperature also influences pathogen-host interactions by affecting pathogen virulence and replication rates. Pathogens often flourish within temperature ranges, and sudden temperature fluctuations can establish conditions conducive to pathogen proliferation and compromise the host's immune defences. This dynamic presents a considerable challenge in aquaculture, where maintaining optimal water temperatures is essential for disease prevention in fish and their overall health.

Table 2.

Impact of temperature on the immune responses of various aquatic species.

Species	Optimal temperature	Effects on the immune system	Reference
Grass carp (Ctenopharyngodon idellus)	High temperatures (varied)	Elevated temperatures adversely impact the expression of immune-related genes	[158]
Pacific oyster, Mediterranean mussel	Varied temperature stress	Temperature fluctuation influenced the immune system	Rahman et al. [159]
Nile Tilapia (Oreochromis niloticus)	Varied (low/high)	Increased temperatures enhanced immune responses	Qiang et al. [160]
Japanese flounder (Paralichthys olivaceus)	Varied (against LCDV virus)	Reduced temperatures diminished immune efficacy in combating viral infections	Xu et al. [161]
Antarctic fish (Harpagifer species)	2 °C - 10 °C	Temperature increase enhanced immune responses	Saravia et al. [162]
Abalone (Haliotis rubra)	Elevated temperatures	Elevated temperatures diminish antibacterial and antiviral defences	Dang et al. [163]
Surf clams (Mactra veneriformis)	Immediate temperature changes	Immediate temperature fluctuations adversely impact immune responses	Yu et al. [164]
Turbot (Scophthalmus maximus)	High temperatures	The skin's immune system suffered when water temperature increase	Huang et al. [165]
Freshwater crayfish (Astacus leptodactylus)	High temperatures	Immune response diminished, increasing the risk of white spot syndrome virus (WSSV).	Jiravanichpaisal et al. [166]
Channel catfish (Ictalurus punctatus)	15–20 °C	Reduced temperatures inhibited immune responses, while a moderate increase promoted immune activity	Martins et al. [167]
Tambaqui (Colossoma macropomum)	Varied temperatures	The immune response was influenced by temperature and environmental pollutants	Salazar-Lugo et al. [168]
Arctic charr (Salvelinus alpinus)	10 °C	The immune response of Arctic charr to vaccination is favorable at temperatures up to 10 °C; however, higher temperatures do not provide further advantages.	Pylkkàet al. [169]
Common carp (Cyprinus carpio L.)	Minimizing temperature fluctuations	The study indicates that reducing temperature fluctuations is essential for preserving immune competence in carp.	Engelsma et al. [170]
Sablefish (Anoplopoma fimbria)	12-14 °C	At 18 °C, immune responses, including lysozyme activity and phagocytosis, were elevated, suggesting an activation of the immune system at increased temperatures.	Kim et al. [171]
Shore crab (Carcinus maenas)	20 °C	A gradual temperature increase from 10 °C to 20 °C significantly elevated circulating haemocyte (immune cell) counts, suggesting enhanced immune activity.	Truscott and White [172]
Sockeye salmon (Oncorhynchus nerka)	8-12 °C	Temperature at 8-12 °C enhances the non-specific immune responses of fish	Alcorn et al. [173]
Surf clams (Mactra veneriformis)	20 °C	Decreased haemocyte proliferation and lysozyme activity may impair the clam's capacity to defend against infections.	Yu et al. [164]
Farrer's scallop Chlamys farreri	< 29 °C	A temperature of 29 °C negatively impacts immune function and energy balance.	Wang et al. [174]
Blue mussels (Mytilus spp.)	5-10 °C	This study demonstrated that temperature influences immune function, with low temperatures enhancing hemocyte health and phagocytosis, whereas high temperatures may induce inflammatory responses and metabolic stress in blue mussels.	Beaudry et al. [175]
Rainbow trout (Oncorhynchus mykiss)	15 °C	Higher temperatures (23 °C) induce immune and metabolic stress, thereby increasing susceptibility to pollutants and parasites.	(2019)
Mediterranean finfish aquaculture	N/A	Temperature influences fish immune function and vulnerability to diseases in Mediterranean aquaculture.	Cascarano et al. [176]
Walbaum (Oncorhynchus mykiss)	10 °C	Temperature significantly influences immune responses and pathogen development, as elevated conditions promote parasite growth and host decline.	Kocan et al. [177]
Catla (Catla catla)	28 °C	Maintaining Catla catla within the temperature range of 25–28 °C is essential for ensuring immune competence, optimal growth, and survival. It is critical to avoid temperatures below 20 °C or above 35 °C to prevent stress and mortality.	Sharma et al. [178]
Mozambique tilapia (Oreochromis mossambicus)	27 °C	Temperature significantly influences immune responses in tilapia, with both low and high temperatures impairing disease resistance. Maintaining the fish at 27 °C reduces physiological stress, thereby enhancing survival rates in both cultured and natural environments.	Ndong et al. [110]
Pufferfish (Takifugu obscurus)	25 °C	Reduced temperature resulted in Immunosuppression diminishes the capacity of fish to combat infections and recuperate from diseases.	Cheng et al. [179]
Pufferfish (Takifugu obscurus)	High temperatures	The immune system is influenced by temperature, as elevated temperatures can induce oxidative stress and lead to potential tissue damage.	Cheng et al. [180]
Manila clam (Ruditapes philippinarum)	18 °C	High temperatures can lead to immune suppression or overactivation, compromising the clam's ability to defend against pathogens and increasing susceptibility to disease and mortality.	Menike et al. [181]
Mytilus coruscus	< 31 °C	Temperatures exceeding 31 °C are associated with increased mortality and impact the immune system.	Li et al. [182]
Polar cod (Boreogadus saida)	4 °C	Increased temperature suggests that increased thermal conditions enhance stress and immune responses.	Kim et al. [183]
Nile tilapia (Oreochromis niloticus)	27.9 °C - 29.4 °C	Temperature around 20.0 °C resulted in higher mortality and reduced the immune system of fish	Qiang et al. [160]
Pacific herring (Clupea pallasii)	12.6 °C	The immune system of Pacific herring is significantly influenced by temperature, which modulates the speed and efficacy of vaccine-induced responses.	Hart et al. [184]
Atlantic salmon (Salmo salar)	16.5 - 17.5 °C	Temperature influences immune function by affecting stress levels, metabolic demand, and susceptibility to pathogens.	Stehfest et al. [185]
Olive flounder (Paralichthys olivaceus)	> 16.5 °C	Temperature influences the immune system by inhibiting growth and immune function; however, taurine supplementation can alleviate these effects, thereby improving the flounder's resistance to cold stress.	Kim et al. [186]
Shell mussel (Mytilus coruscus)	25 °C	Temperature significantly influences the immune system, as extended exposure to high temperatures diminishes immune efficiency and enhances cellular damage.	Wu et al. [187]
Orange-spotted grouper (Epinephelus coioides)	28 °C	Temperature has a significant impact on the immune system, where cold stress induces immunosuppression, inflammation, and apoptosis.	Sun et al. [111]
Hard clams (Mercenaria mercenaria)	21 °C	Temperature has a significant impact on the immune system through the modulation of gene expression associated with immune recognition, pathogen defense, and oxidative stress.	Wang et al. [188]
Diamond-backed terrapins (Malaclemys terrapin)	34 °C	Elevated temperatures, approaching 34 °C, are likely to improve immune competence by facilitating accelerated metabolism and more effective physiological processes.	Tamplin et al. [189]
Thick-shelled river mussel (Unio crassus)	17 °C	Increased temperatures can lead to either immune suppression or hyperactivation, potentially impacting the host's capacity to endure the parasitic phase.	Taeubert et al. [190]
Sea cucumber (Holothuria scabra)	27 °C	At elevated temperatures, low levels of reactive oxygen species (ROS) and minimal oxidative damage were noted, indicating that the immune system efficiently mitigated stress during the experiment.	Kamyab et al. [191]
Pacific white shrimp (Litopenaeus vannamei)	28 °C	The immune system is influenced by temperature through modifications in the expression of heat shock proteins and genes associated with apoptosis.	Peng et al. [192]
Oscar (Astronotus ocellatus)	22–27 °C	High temperatures induce elevated stress in fish, which may lead to potential liver damage and impaired immune function, thereby increasing their vulnerability to disease.	Esmaeili et al. [193]

<: Below; >: Higher.

One notable consequence of temperature-driven immune modulation in fish is the phenomenon known as Winter Syndrome, first described by [194]. This condition occurs with exposure to low water temperatures, impairing both innate and adaptive immune functions in aquatic species [195]. Reduced phagocytic activity, diminished lysozyme levels, and suppressed cytokine expression are frequently observed. The immunosuppressive condition heightens the susceptibility of fish to opportunistic bacterial and viral infections, including Aeromonas hydrophila and Vibrio spp., particularly in aquaculture systems without thermal regulation. Winter Syndrome illustrates the manner in which seasonal abiotic stressors can exacerbate biotic challenges, underscoring the necessity for temperature regulation and immunostimulatory strategies in colder periods.

Understanding the relationship between temperature and immune responses is essential in aquaculture and conservation. Global climate change modifies temperature patterns in aquatic ecosystems, potentially intensifying disease dynamics and elevating the risk of pathogen outbreaks in wild populations, thereby jeopardising biodiversity. Regulating temperature in controlled environments (aquaculture systems) can boost immune resilience and minimise disease occurrence. Temperature significantly influences the immune function of aquatic animals, and its effects are increasingly concerning, given the changing environmental conditions.

Salinity

Salinity is a critical abiotic factor in aquatic environments that significantly influences the immune responses of aquatic animals. Fish and invertebrates frequently experience variations in salinity, which can disturb their physiological homeostasis and subsequently affect their immune function [[196], [197], [198]]. The impact of salinity on immune function is primarily mediated by mechanisms associated with osmotic balance, ion regulation, and cellular stress (Fig. 3). Elevated salinity (hyperosmotic conditions) often results in cellular dehydration, impairing immune cells' proliferation and function, including leukocytes. Lu et al. [199] found that elevated salinity levels diminished leukocyte phagocytic activity, reduced cytokine production, and compromised the overall immune response in fish. Conversely, low salinity (hypoosmotic conditions) may lead to cellular swelling and stress, thereby initiating an acute immune response. Prolonged exposure to these conditions can lead to immune suppression. For instance, euryhaline fish exhibited elevated levels of stress-related proteins in response to hypoosmotic stress, including heat shock proteins and pro-inflammatory cytokines [200].

Fig. 3.

Salinity effects on fish immune system [[199], [201], [202], [203], [204]].

The relationship between salinity and immunity is often mediated by ionic imbalance, oxidative stress, and endocrine responses. Salinity stress alters ionic balance, forcing aquatic animals to invest more energy towards osmoregulation compared to immune defence [205]. Increased salinity also causes oxidative stress that is harmful to immune cells and their functions [206]. Stress hormones such as cortisol are activated by salinity changes, suppressing immune responses, diminishing leukocyte activity, and decreasing the production of immune proteins [207].

Table 3 presents how salinity significantly influences the immune responses of aquatic animals. Euryhaline species that can withstand a wide range of salinities have developed adaptive immune mechanisms. Atlantic salmon (Salmo salar) demonstrated an upregulation of immune-related genes during the transition from freshwater to seawater, notably increasing AMPs [208]. In contrast, stenohaline species, which flourish within a limited salinity range, exhibit increased susceptibility to immune suppression when subjected to salinity stress. Wang et al. [209] reported that Pacific white shrimp (Litopenaeus vannamei) exhibit reduced hemocyte activity and immune-related gene expression under hyper- and hypo-osmotic conditions, suggesting impairments in the shrimp's infection resistance due to salinity fluctuations.

Table 3.

Effects of salinity on immune responses across various aquatic species.

Species	Best salinity	Effects on the immune system/Findings related to salinity and immunity	Reference
Scatophagus argus	25 ppt	Elevated immune responses were observed, characterized by increased expression of cytokine genes, enhanced leukocyte proliferation, and more robust immune parameters during infection.	Lu et al. [199]
Syngnathus typhle	Ambient salinity	Enhances immune health through increased activity and proliferation of immune cells.	Birrer et al. [196]
Mytilus edulis	15 ppt	Reduced salinity immune responses are significantly suppressed, leading to a reduction in both functional and molecular immune characteristics.	Wu et al. [210]
Nibea albiflora	6-30 ppt	High salinity (42 ppt) induces stress, adversely affecting immune enzyme activity, growth, and gut health.	Tian et al. [211]
Oreochromis niloticus	16 ppt	At higher ppt levels, the immune systems of the fish experienced stress, resulting in an increased susceptibility to illness.	El-Leithy et al. [212]
Pangasianodon hypophthalmus	10 ppt	Salinity affects immune ability and may decrease the resilience of catfish to infections, including Edwardsiella ictalurid.	Schmitz et al. [213]
Alosa sapidissima	14-21 ppt	14 to 21 ppt enhanced immune respond, better growth, improved enzyme activity and optimal fatty acid composition.	Liu et al. [214]
Oreochromis niloticus	0-10 ppt	Higher ppt inhibited immune relayed genes of IgM, IL-1β, and IFN-γ	Wang et al. [215]
Takifugu fasciatus	10 ppt	Low salinity supporting the immune system and reducing the physiological stress of fish	Wen et al. [216]
Acanthopagrus latus and Lates calcarifer	6-12 ppt	Rising salinity influenced the humoral immune responses of fish.	Mozanzadeh et al. [217]
Procambarus clarkii	0-2 ppt	Higher salinity effected the immune system of fish	Xiao et al. [218]
Portunus trituberculatus	31 ppt	Lower salinity induced temporary immune supression	Wang et al. [219]
Anguilla japonica	<0.5 ppt	Freshwater condition improve immune-related gene expression	Gu et al. [220]
Cyprinus carpio	0-10 ppt	High salinity effects the immune and physiological stress of fish	Dawood et al. [221]
Scophthalmus maximus	24-30 ppt	High salinity effect the immune system, particularly IgM expression in the kidney.	Huang et al. [222]
Anoplopoma fimbria	31.5-35 ppt	Higher salinity improves immune system of fish	Kim et al. [171]
Echinometra lucunter	35 ppt	Reduced salinity may trigger oxidative stress, while elevated salinity can result in mitochondrial dysfunction.	Honorato et al. [223]
Eriocheir sinensis	8 ppt	High salinity effect immune system of the crab	Yang et al. [224]
Gadus morhua	10 ppt	The density did not affect the immune system of fish; however, 10 ppt is the optimal value for growth.	Árnason et al. [207]
Litopenaeus vannamei	1-5 ppt	Low salt-tolerant hybrid shrimp demonstrate enhanced immune performance and antioxidant capacity.	Ye et al. [225]
Notopterus chitala	0-3 ppt	Salinity exceeding 6 ppt can result in considerable oxidative damage and immune suppression.	Moniruzzaman et al. [226]
Litopenaeus vannamei	25-30 ppt	Salinity at 25-30 ppt increase the immune respond and disease resistance	Wang and Chen [227]
Penaeus monodon	20 ppt	Salinity at 20 ppt produced optimal growth, survival, and a stable immune response.	Rahi et al. [228]
Acanthopagrus schlegelii	22 ppt	At a salinity of 22 ppt, fish experience reduced physiological stress and enhanced immune function, allowing them to survive even at lower salinities of 4-5 ppt.	Li et al., [229]
Haliotis diversicolor supertexta	30 ppt	Salinity at 30 ppt enhances immune system of Haliotis diversicolor supertexta	Cheng et al. [230]
Dicentrarchus labrax	6-12 ppt	Results indicate that Dicentrarchus labrax acclimatized at intermediate salinities (6 and 12 ppt) exhibit superior performance during exposure to extreme cold conditions (8 °C).	Jakiul Islam et al. [231]
Aquarana catesbeiana	2-4 ppt	Higher salinity can induce oxidative stress and potential immune suppression	Zheng et al. [232]
Litopenaeus vannamei	36 ppt	Salinities under 36 ppt are recommended for L. vannamei aquaculture to enhance immune health and metabolic balance.	Long et al. [233]
Haliotis discus discus	25 ppt	Keeping salinity levels below this threshold (25 ppt) may enhance immune function and overall health in disk abalone.	De Zoysa et al. [234]
Procambarus clarkii	6 ppt	High salinity up to 18 ppt cause immune disruption and metabolic stress	Luo et al. [235]
Ctenopharyngodon idella	2 ppt	Higher salinity (6 ppt) lead to immune suppression and decline in growth performance	Liu et al. [236]
Larimichthys polyactis	22.1 ppt	The fish can adapt at low salinity, but salinity at 22.1 ppt improve immune system and physiological function	Mengjie et al. [237]
Scapharca subcrenata	22 ppt	Salinity changes effect the immune system, growth performance and physiological balance of Scapharca subcrenata	Mo et al. [238]
Oreochromis spp.	5-10 ppt	Moderate salinity improve immune responses and health of fish	Ulkhaq et al. [239]
Pseudosciaena crocea	5-10 ppt	High salinity (15-20ppt) is not suitable for growth and immune system	Wang et al. [240]
Litopenaeus vannamei	56 ppt	A salinity level of 56 ppt is recommended to ensure immune stability and minimize physiological stress.	Shen et al. [241]
Cherax quadricarinatus	5 ppt	Salinity at 5 ppt improve the immune function, antioxidant activity and gut health	Liu et al. [242]
Litopenaeus vannamei	0-4 ppt	Rearing fish with multispecies of probiotic is recommend at low salinity (0-4 ppt)	Zannat et al. [243]
Oreochromis niloticus	0-10 ppt	High salinity levels (15-20 ppt) impact the health and growth of fish when dietary supplementation with Aspergillus oryzae is administered.	Shukry et al. [244]
Macrobrachium rosenbergii	13 ppt	Salinity of 13 ppt is recognized as optimal for enhancing growth, immunity, enzyme activity, and successful larval development in Macrobrachium rosenbergii	Wei et al. [245]
Sinonovacula constricta	30 ppt	Exceeding 35 ppt has a detrimental impact on health and growth performance.	Cao et al. [246]
Ruditapes philippinarum	23.3-31.1 ppt	Low salinity (15 ppt) enhances susceptibility to metabolic and oxidative disruptions.	Wu et al. [247]
Oreochromis niloticus	4-8 ppt	Salinity levels of 4 to 8 ppt may partially reduce ammonia toxicity and enhance antioxidant defense mechanisms.	Motamedi-Tehrani et al. [248]
Eriocheir sinensis	≤ 6 ppt	Higher salinity (≥ 12 ppt) lead to physiological stress and increase mortality rate	Zhang et al. [249]
Penaeus vannamei	40-47 g/L	High salinity affected the amino acid composition in the body, which directly influences the immune system of fish.	Li et al. [250]
Selenotoca multifasciata	5 ppt	High salinity increased physiological strain and greater stress response	Liu et al. [251]
Oryzias melastigma	15 ppt	Improve growth and health performance	Li et al. [252]
Giant clams (Bivalvia: Tridacnidae)	34 ppt	Reduced salinities adversely affected growth and long-term health conditions.	Lee et al. [253]

It is clear that environmental challenges such as climate change and human activities may increase salinity variability in aquatic ecosystems. Therefore, evaluating the relationship between salinity and immune function is crucial for effectively managing aquaculture systems. Future research should focus on examining species-specific adaptations to salinity stress and exploring strategies to improve immune resilience in aquaculture via environmental management or selective breeding.

Oxygen levels (Hypoxia)

Hypoxia is characterised by oxygen levels falling below the normal threshold (< 2 mg/L), profoundly affecting aquatic organisms' physiological and immune responses [254]. Aquatic animals under hypoxia are pressured to focus on physiological responses aimed at maintaining oxygen homeostasis, compromising their immune function and increasing their susceptibility to infections. Moreover, hypoxia modifies immune-related gene expression, diminishing the function of critical immune cells (macrophages, neutrophils) and decreasing the synthesis of reactive oxygen species (ROS) vital for pathogen eradication [255,256]. Aquatic animals exposed to hypoxic conditions frequently exhibit diminished immune defences, rendering them more vulnerable to bacterial, viral, and parasitic infections, as illustrated in Table 4.

Table 4.

Oxygen levels and immune responses in aquatic species under hypoxic conditions.

Species	Optimal oxygen level	Critical hypoxia threshold	Immune response under hypoxia	Reference
Salmo salar	> 95 % saturation (∼8.3 mg/L)	70 % saturation (∼5.9 mg/L)	Decreased expression of immune-related genes in low oxygen conditions, compromised stress responses, and inflammation associated with prolonged hypoxia	Beemelmanns et al. [257]
Cyprinus carpio	6–8 mg/L	∼3 mg/L	Improved hypoxia tolerance is associated with a slight decrease in immune function	Cerra et al. [258]
Danio rerio	6–7 mg/L	< 3 mg/L	Enhanced survival rates in chronic hypoxia and improved immune response adaptation during juvenile stages following prolonged exposure	Chun and Kim [259]
Pseudobagrus ussuriensis	Above 6 mg/L	1.5 mg/L	Acute hypoxia results in immune suppression, skin damage, and heightened susceptibility to infections following reoxygenation	Liu et al. [260]
Sander lucioperca	8.3 mg/L	∼3.2 mg/L	Chronic hypoxia affects leukocyte count, impairs acute inflammatory responses, and increases susceptibility to infections	Huo et al. [261]
Apostichopus japonicus	6–8 mg/L	1.5–2 mg/L	Reduced activities of antioxidant enzymes, diminished immune defences, lowered oxygen uptake, and increased oxidative stress	Huo et al. [261]
Ictalurus punctatus	∼6 mg/L	< 2 mg/L	Elevated heart rate and enhanced oxygen extraction support immune function; however, these mechanisms are impaired under prolonged hypoxia	Cerra et al. [258]
Carassius auratus	> 5 mg/L	< 1 mg/L	Acute hypoxia promotes cardiovascular adaptation; however, it may lead to a suppression of immune function over an extended period	Cerra et al. [258]
Hypophthalmichthys molitrix	> 6 mg/L	< 0.76 mg/L	Elevated oxidative stress and immune suppression, particularly in hepatic and brain tissues, lead to compromised physiological function	Wang et al. [262]
Scylla paramamosain	> 6 mg/L	1 mg/L	Reduced antioxidant capacity and altered glutaredoxin activity in gills diminished immune defence against pathogens.	Jie et al. [263]
Ruffe and Flounder	> 6 mg/L (normoxia)	< 1.5 mg/L	Tissue damage and downregulation of immune genes in the gills and heart, alongside diminished metabolic and immune functions, occur under conditions of severe hypoxia	Tiedke et al. [264] Karpowicz et al. [265]
Benthic organisms (Coastal)	> 4–5 mg/L	< 2 mg/L	Reduction in biodiversity, immune system failure, and behaviour changes when animals relocate or die from oxygen loss	Rabalais et al. [266]
Zooplankton (Lake ecosystems)	> 5 mg/L	< 2 mg/L	Reduced immunological responses and physiological stress, severe hypoxia collapses communities	Karpowicz et al. [265]

<: Less than; >: More than

The innate immune system is susceptible to hypoxic stress. Oxygen-dependent mechanisms are impaired in low-oxygen environments. For instance, reduced ROS production decreased the efficacy of macrophages and neutrophils in eliminating pathogens. Hypoxia-induced immune suppression has been documented in O. niloticus (Nile tilapia) [267]. Wang et al. [268] revealed that prolonged hypoxia stress diminished phagocytic activity and heightened vulnerability to Streptococcus iniae infections. Likewise, the adaptive immune system, which includes lymphocytes such as T and B cells, is also compromised during hypoxia. Hypoxia hampers lymphocyte proliferation, antibody production, and dendritic cell maturation, essential for antigen presentation and immunological memory development [269]. This disruption diminishes the capacity of aquatic animals to generate a robust adaptive immune response to pathogens.

The hypoxia-inducible factor (HIF) pathway is crucial in regulating immune changes at the molecular level during hypoxia. Stabilising HIF-1α in hypoxic conditions activates genes that regulate oxygen homeostasis and facilitate metabolic adaptation. This shift frequently compromises immune function, as metabolic resources are redirected towards survival instead of maintaining immune competence [270]. In fish and other aquatic animals, sustained activation of the HIF pathway during chronic hypoxia results in immune suppression, diminishing the organism's overall fitness and capacity to respond to pathogenic threats. Consequently, overcrowding and poor water quality can worsen hypoxia and result in disease outbreaks in natural and aquaculture populations [271].

The implications of hypoxia-induced immune suppression in aquatic environments are substantial, particularly regarding climate change and anthropogenic oxygen depletion. Increasing hypoxic conditions in aquatic habitats, driven by eutrophication and elevated water temperatures, may impair the disease resistance of aquatic organisms, potentially resulting in population declines and disruptions to ecosystem equilibrium. Investigating the molecular and physiological mechanisms through which hypoxia influences immune function in aquatic animals is essential for formulating mitigation strategies to enhance these organisms' resilience to environmental stressors.

Pollutants and chemicals

Aquatic environments are increasingly affected by various pollutants, such as heavy metals, pesticides, and pharmaceuticals, which can notably impair the immune systems of aquatic organisms. A summary of the effects of pollutants and chemicals on the immune systems of aquatic animals can be found in Table 5. Heavy metals, including cadmium (Cd), lead (Pb), mercury (Hg), and copper (Cu), are immunotoxic, causing oxidative stress and dysfunction in immune cells. Cadmium exposure in O. niloticus (Nile tilapia) diminished phagocytic activity and ROS generation, which is essential for innate immune defence [272]. Similarly, Mytilus galloprovincialis (marine mussels) exposed to cadmium exposure demonstrated impaired hemocyte function in their immune responses [273,274]. Mercury, especially in its methylmercury (MeHg) form, inhibited immune responses in Danio rerio (zebrafish) by influencing T-cell proliferation and antibody production [275,276]. Meanwhile, lead exposure decreased cytokine production critical for initiating immune responses, including interleukin-1β (IL-1β) and tumour necrosis factor-alpha (TNF-α) [277,278].

Table 5.

Effects of pollutants and chemicals on the immune systems of aquatic animals.

Species	Pollutant/Chemical	Effects on the immune system	Reference
Common carp (Cyprinus carpio)	Chlorpyrifos	Inhibition of macrophage function and decreased lysozyme synthesis, compromising innate immune responses	Taheri Mirghaed et al. [279]
Rainbow trout (Oncorhynchus mykiss)	Pyrethroids	Impairment of humoral immunity and a decrease in antibody production	Major and Brander [280]
African clawed frog (Xenopus laevis)	Atrazine	Endocrine disruption, diminished immune cell proliferation, and modified cytokine profiles	Galbiati et al. [281]; Zhang et al. [282]
Atlantic salmon (Salmo salar)	Antibiotics	A decrease in gut microbial diversity leads to compromised immune defences	Wang et al. [283]; Wang et al. [284]
Grass shrimp (Palaemonetes pugio)	Fluoxetine	Reduced antimicrobial peptide release and impaired hemocyte activity	Coates and Costa-Paiva [285]; Alboni et al. [286]
European sea bass (Dicentrarchus labrax)	Diclofenac (NSAID)	Inhibition of prostaglandin production leads to decreased inflammatory and phagocytic activities	Courant et al. [287]
Rainbow trout (Oncorhynchus mykiss)	Cadmium	Oxidative stress leads to damage in immune cells, resulting in impaired immune function	Eskander and Saleh [288]
Atlantic cod (Gadus morhua)	Cortisol (stress hormone, induced by pollutants)	Increased cortisol concentrations result in immunosuppression.	Campbell et al. [289]
Mediterranean mussel (Mytilus galloprovincialis)	Various NSAIDs (e.g., diclofenac)	Decreased immune responses, encompassing gill integrity and phagocytic activity	Chaabani et al. [290]; Courant et al. [287]
European plaice (Pleuronectes platessa)	Heavy metals (cadmium)	Impaired innate immunity encompasses alterations in lysozyme levels and phagocytic activity	Eskander and Saleh [288]
Mummichog (Fundulus heteroclitus)	Polycyclic aromatic hydrocarbons (PAHs)	Impairment of immune cell function and reduced susceptibility to infections	Pijanowski et al. [291]

NSAID: Non-steroidal anti-inflammatory drugs

Pesticides, such as organophosphates and pyrethroids, are also immunotoxic to aquatic organisms. Chlorpyrifos, an extensively utilised organophosphate insecticide, adversely impacted the innate immunity of Cyprinus carpio (common carp) by inhibiting macrophage function and diminishing lysozyme synthesis [279]. Meanwhile, pyrethroid exposure impaired the humoral immunity in Oncorhynchus mykiss (rainbow trout), reducing their antibody production [280]. In addition, herbicides, such as Atrazine, disrupted endocrine functions in amphibians, particularly Xenopus laevis, leading to impaired immune cell proliferation and altered cytokine profiles [281]. One of the most recent risks of immunotoxic aquatic pollutants is pharmaceuticals. Antibiotics, including tetracyclines and fluoroquinolones, can alter the microbiome of aquatic animals, which is crucial for immune regulation. Antibiotic exposure in Salmo salar (Atlantic salmon) reduces gut microbial diversity, impairing their immune defences [[283], [284]]. Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, inhibit prostaglandin production, impair inflammatory responses and reduce phagocytic activity in fish [[287], [290]]. Meanwhile, antidepressants such as fluoxetine have been shown to impair hemocyte activity in Palaemonetes pugio (grass shrimp), reducing AMP release and increasing susceptibility to pathogens [285].

The mechanisms responsible for these immunotoxic effects typically include the induction of oxidative stress, disruption of endocrine pathways, and interference with immune signalling processes. Oxidative stress, often induced by heavy metals and pesticides, disrupts immune cell function and diminishes its ability to combat infections [288,292]. Pollutants can activate the hypothalamic-pituitary-interrenal (HPI) axis, increasing cortisol levels linked to immunosuppression [[289], [293]]. Endocrine-disrupting chemicals (EDCs), including atrazine, exacerbate immune dysfunction by modifying cytokine signalling pathways, compromising innate and adaptive immune responses. Therefore, it is important to understand pollutants' impact on aquatic organisms' immune health, which potentially influences population dynamics and ecosystem stability.

pH levels

pH levels significantly affect the immune responses of aquatic animals due to ocean acidification due to elevated atmospheric carbon dioxide (CO₂) (Table 6). The dissolution of CO₂ in seawater results in carbonic acid formation, which decreases pH levels and can adversely impact the physiological and immunological health of numerous species. Research indicates that Crassostrea gigas (Pacific oyster) exhibited reduced hemocyte activity and impaired phagocytic responses under acidic conditions, which compromised their innate immune function and heightened their susceptibility to pathogens [[294], [295], [296]]. Mytilus edulis (blue mussel) susceptibility to bacterial infections and mortality rates increased significantly in acidified waters, illustrating the correlation between compromised immune responses and increased vulnerability [[297], [298], [299]].

Table 6.

Impact of pH levels on the immune responses of various aquatic species.

Species	Optimal pH	Stressful pH	Effect on the immune system	Reference
Pacific white shrimp (Litopenaeus vannamei)	7.5–8.5	< 7.0	Decreased hemocyte activity and dysregulation of the Na+/H+ exchanger under acidic stress negatively affect immune response	Li et al. [300]; Townhill et al. [301]
Blue mussel (Mytilus edulis)	7.8–8.3	< 7.6	Decreased phagocytic ability of hemocytes increased mussel’s vulnerability to infections in acidic environments	Guo et al. [298]; Mackenzie et al. [299]
Pacific oyster (Crassostrea gigas)	7.8–8.4	< 7.6	Reduced expression of immune genes and compromised hemocyte function hinder pathogen defence	Dineshram et al. [302]; Gazeau et al. [297]
Arctic copepod (Calanus glacialis)	∼8.0	< 7.6	Decreased metabolic rates and diminished immune function adversely affected survival in acidic environments	Thor et al. [303]
Channel catfish (Ictalurus punctatus)	7.5–8.5	< 7.0	Decreased white blood cell and phagocytic activity	Sánchez-Martínez et al. [304]; Zhao et al. [305]
European sea bass (Dicentrarchus labrax)	7.8–8.3	< 7.4	Disruption of skin mucosal immunity increased susceptibility to infections, particularly Vibrio harveyi	Kataoka and Kashiwada [306]
Pufferfish (Takifugu rubripes)	7.6–8.2	< 7.0	A decrease in haematological parameters (RBC, haemoglobin) was attributed to oxidative stress due to low pH exposure	Xu et al. [307]
Thick shell mussel (Mytilus coruscus)	7.8–8.3	< 7.3	Decreased haemocyte count, impaired phagocytosis, diminished esterase activity at low pH, and elevated reactive oxygen species levels	Wu et al. [308]
Common carp (Cyprinus carpio)	7.0–8.5	< 6.5	Lower pH levels of ammonia elevate oxidative stress and induce immune suppression	Xu et al. [307]
Pipefish (Syngnathus typhle)	7.5–8.0	< 7.3	Immunosuppression and heightened vulnerability to pathogens due to ocean acidification	Tort and Balasch [309]
Amur minnow (Phoxinus lagowskii)	N/A	Higher Ph	The pH, especially in the context of saline-alkaline stress, influences the immune system of fish.	Zhou et al. [198]
Spotted babylon (Babylonia areolata)	7.5–8.5	N/A	Ph influence the immune system of spotted babylon	Ding et al. [310]
Chinese mitten crab (Eriocheir sinensis)	7.5–8.5	N/A	Low pH impairs the Toll-like receptor (TLR) pathway, thereby diminishing the immune defense of crabs.	Zhang et al. [311]
Common carp (Cyprinus carpio); Mrigal (Cirrhinus mrigala); Rohu (Labeo rohita)	8.0	9.0	The pH level impacts the immune system of fish by modulating the activity of non-specific immune enzymes present in skin mucus.	Sridhar et al. [312]
White shrimp (Litopenaeus vannamei)	8.0–8.1	> 8.1	Shrimp raised at pH 8.1 demonstrated significantly enhanced immune activation and immune parameters relative to those raised at pH 6.8.	Chen et al. [313]
White shrimp (Litopenaeus vannamei)	7.8–8.2	>8.2	Shrimp subjected to pH 6.5 (low) and pH 10.1 (high) demonstrated reduced immune responses relative to those maintained at pH 8.2 (control).	Li and Chen [314]
Nile tilapia (Oreochromis niloticus)	7.0–8.0	N/A	pH influences the immune system of Nile tilapia (Oreochromis niloticus)	Dominguez et al. [315]
Rohu (Labeo rohita)	6.5–7.5	< 6.5	Fish reared at pH 7.0 demonstrated superior immune and growth performance, indicating that this pH level is optimal for Labeo rohita.	Singh et al. [316]
Indian white shrimp (Fenneropenaeus indicus)	7.8–8.5	< 7.0	Low pH exposure significantly compromised immune functions in F. indicus.	Sharma et al. [317]

N/A: Not available.

Acidification also influences the development of immune systems during the early life stages of aquatic species. For instance, Ostrea edulis (European flat oyster) larvae cultivated in low pH environments demonstrated modified immune gene expression, which may affect their health and survival in the long term [318,319]. Furthermore, pH alterations directly impact immunity and disrupt metabolic processes, leading to physiological stress [320,321]. These findings indicated the cumulative impact of compromised immune responses due to fluctuating pH levels on aquatic species, manifesting as increased disease susceptibility and altered metabolic processes. Investigating these dynamics could aid stakeholders in predicting and overcoming the effects of climate change on marine ecosystems and their resident organisms.

Ultraviolet radiation

Ultraviolet (UV) radiation can significantly impact the immune responses of aquatic animals, as shown in Table 7. The UV-B (280–320 nm), in particular, can penetrate aquatic ecosystems at various levels depending on water clarity and depth. High UV exposure in aquatic animals causes oxidative stress, DNA damage, and compromised immune responses essential to combat pathogens and environmental stressors [[322], [323], [324]]. The UV-induced oxidative stress produces ROS that is harmful to cellular components, including DNA, proteins, and lipids, impairing cellular functions [325]. In fish and marine invertebrates, oxidative damage hampered immune parameters, such as phagocytic cell activity, AMP production, and immune competence. For instance, O. mykiss (rainbow trout) exposed to UV-B exhibited reduced lymphocyte proliferation and poor macrophage function, thereby diminishing their ability to combat pathogens [[323], [326]].

Table 7.

Effects of ultraviolet radiation on the immune responses of various aquatic species.

Aquatic species	Type of UV radiation	Effects on the immune system and other biological responses	References
Rainbow trout (Oncorhynchus mykiss)	UV-B	Reduced lymphocyte proliferation; compromised macrophage activity; heightened vulnerability to pathogens	Fajardo et al. [326]
Pacific oyster (Crassostrea gigas)	UV-B	Reduced lymphocyte proliferation; compromised macrophage activity; heightened vulnerability to pathogens	Mello et al. [327]
Water flea (Daphnia magna)	UV-B	Increased oxidative stress; modified immune response resulting in increased vulnerability to pathogens; diminished reproductive success	Ivanina et al. [328]
Seahorse (Hippocampus erectus)	UV-A and UV-B	Modified immune responses result in decreased resistance to viral infections and may cause endocrine disruption	Song et al. [329]
Rohu fish (Labeo rohita)	UV-B	Ultraviolet B radiation adversely impacts immune responses, diminishing defence mechanisms in aquatic larvae	Singh et al. [330]
High-altitude fish species	UV-B	Inhibition of primary and secondary immune responses due to UV-B exposure	Subramani et al. [331]
Fish (species unspecified)	UV-A and UV-B	UV-B exposure modified immune system function in fish, resulting in immunosuppression	Salo et al. [332]
Zebrafish (Danio rerio)	UV-B	UV-B radiation, in conjunction with varying temperatures, influenced stress and innate immune responses.	Icoglu Aksakal and Ciltas [333]
Various fish species	UV-B	UV-B irradiation impaired non-specific and specific immune responses in fish	Sharma and Chakrabarti [334]
Teleost fish	UV-A and UV-B	Ultraviolet radiation negatively affected immune function and heightened disease susceptibility in fish	Lawrence et al. [335]
Three-spined stickleback (Gasterosteus aculeatus)	UV-B	UV-B exposure reduced innate and adaptive immune responses in sticklebacks	Vitt et al. [336]
Common carp (Cyprinus carpio) and Rainbow trout (Oncorhynchus mykiss)	UV-B	UV-B influenced specific and nonspecific immune responses in fish	Markkula et al. [337]
Marine zooplankton and ichthyoplankton	UV-A and UV-B	Ultraviolet radiation negatively affected immune function during the early developmental stages of marine organisms	Browman et al. [338]
Three-spined sticklebacks (Gasterosteus aculeatus)	UV-B	Ultraviolet-B (UVB) radiation influences the immune system of fish by lower splenosomatic index and higher granulocyte to lymphocyte ration	Vitt et al. [336]
European seabass (Dicentrarchus labrax)	UV-B	Exposure of European seabass (Dicentrarchus labrax) to UVB radiation resulted in alterations in humoral immune parameters, indicating immune system modulation across all UVB doses (low, moderate, and high).	Alves et al. [339]
Gilthead Seabream (Sparus aurata)	UV-B	UVB exposure resulted in decreased total anti-protease and total peroxidase activities, indicating a modulation of the innate immune system.	Alves et al. [340]
Atlantic Salmon (Salmo salar)	UV-B	Effect the plasma lgM levels, lysozyme activity and complement bacteriolytic activity	Jokinen et al. [341]
Indian major carp (Catla catla)	UV-B	UVB radiation resulted in a marked reduction of lysozyme levels in the larvae of Catla catla.	Sharma et al. [342]
African catfish (Clarias gariepinus)	UV-A	Exposure to UV-A resulted in diminished immune responses in African catfish (Clarias gariepinus), as indicated by: 1. A reduction in lysozyme (LYZ) activity, which serves as a marker for non-specific immune function; 2. A decrease in phagocytic activity (PhA), essential for pathogen defense.	Hamed et al. [343]
Rutilus roach (Rutilus rutilus)	UV-B	UVB irradiation resulted in decreased activity of neutrophils and macrophages in Rutilus rutilus	Salo et al. [344]
Atlantic Salmon (Salmo salar)	UV-B	Increased UVB radiation influenced plasma immunoglobulin levels, which are essential for the adaptive immune response.	Jokinen et al. [345]
Senegalese sole (Solea senegalensis)	UVR	Increase oxidative stress resulted effects the immune response of fish by damaging the cells and tissues.	Araújo et al. [346]
African catfish (Clarias gariepinus)	UV-A	UV-A radiation adversely affects the immune system of Clarias gariepinus through the induction of oxidative stress, hormonal imbalance, and tissue damage.	Ibrahim [347]
Rainbow trout (Oncorhynchus mykiss)	UVR	Ultraviolet radiation influences the immune response of rainbow trout by diminishing phagocytic activity while not significantly affecting T lymphocyte proliferation.	Hébert et al. [348]
Rainbow Trout (Oncorhynchus mykiss)	UV-B	UVB radiation influences the immune system of rainbow trout, leading to a gradual decrease in their resistance to parasitic and bacterial infections.	Markkula et al. [349]
Shrimp (Litopenaeus vannamei)	UV-A/ UV-B	Ultraviolet radiation, specifically UVA, has a beneficial effect on immune responses and growth in Litopenaeus vannamei through the enhancement of antioxidant enzyme activity and the reduction of apoptosis-related gene expression.	Fei et al. [350]
European sea bass (Dicentrarchus labrax)	UVR	Ultraviolet (UV) radiation affects the immune system, particularly in the context of developing a UV-inactivated viral vaccine.	Valero et al. [351]
Pacific White Shrimp (Penaeus vannamei)	UV-A	Increased concentrations of acid phosphatase (ACP), phenol oxidase (PO), and lysozyme (LZM) serve as significant indicators of innate immunity.	Wang et al. [352]
Atlantic Salmon (Salmo salar)	UV-B	The modifications in fatty acid composition resulting from UVB exposure and temperature stress may indirectly affect immune function and overall health in Atlantic salmon.	Arts et al. [353]
Common carp (Cyprinus carpio)	UVR	Ultraviolet (UV) radiation exerts an indirect influence on the immune system of fish through the induction of oxidative stress.	Britto et al. [354]
Rainbow Trout (Oncorhynchus mykiss)	UVR	The detrimental impacts of UV light on the skin of rainbow trout can indirectly impair immune function by compromising the skin, an essential barrier against infection.	Bullock and Coutts [355]
Caspian Sea Salmon (Salmo trutta caspius)	UVR	Ultraviolet (UV) radiation indirectly affects the immune system by damaging the skin, which is essential for the defense mechanisms in fish.	Ghanizadeh Kazerouni† and Khodabandeh [356]
Intertidal fish	UVR	The physiological effects may indirectly influence the immune system by undermining overall health and energy distribution, thereby increasing the fish's vulnerability to disease.	García-Huidobro et al. [357]
Rainbow trout (Oncorhynchus mykiss)	UV-B	Ultraviolet-B (UVB) radiation affects the immune system of fish indirectly by causing damage to skin and tissues essential for defense mechanisms.	Abedi et al. [358]
African Catfish (Clarias gariepinus)	UV-A	Ultraviolet-A (UVA) radiation affects the immune system of fish, primarily characterized by physiological and biochemical alterations.	Sayed et al. [359]
Atlantic Cod Larvae (Gadus morhua)	UVR	Behavioural and survival impairments in larval cod resulting from UV exposure may indirectly influence overall health and resilience, potentially impacting immune function.	Fukunishi et al. [360]
Freshwater Carp (Labeo rohita)	UV-B	Ultraviolet-B (UV-B) radiation affects the immune system of fish, demonstrated by alterations in biochemical and physiological markers following UV-B exposure.	Singh et al. [361]

UV-A: Ultraviolet-A (320-400 nm); UV-B: Ultraviolet-B (280-320 nm); UVR: Ultraviolet radiation

Bivalves are marine invertebrates that are susceptible to UV-induced immunosuppression. Studies on C. gigas (Pacific oyster) indicated that UV-B radiation exposure adversely impacted hemocyte activity, reducing phagocytosis and pathogen elimination [328]. Moreover, UV radiation can alter the immune-related gene expression equilibrium, reducing the ability to respond to bacterial infections. Reports have also revealed that UV radiation directly and indirectly influences immune function by modifying microbial communities in aquatic ecosystems [362]. These alterations increased pathogen diversity, which further strained the immune systems of aquatic animals. Stressors and UV-induced immunosuppression may increase the vulnerability of aquatic species to diseases, particularly in areas where ozone depletion enhances UV-B penetration into the water column. Therefore, it is crucial for researchers to find a solution for long-term ecological consequences of UV-induced immune suppression.

Interaction between biotic and abiotic factors

The interaction between biotic and abiotic factors influences the immune function of aquatic species, leading to synergistic or antagonistic effects. Biotic factors, such as pathogens, parasites, and interspecies interactions, directly affect immune responses by triggering various defence mechanisms, including inflammation and the synthesis of antimicrobial peptides. Meanwhile, abiotic factors (temperature, salinity, pH, and pollutants) impact the efficacy of their immune responses. At higher temperatures, pathogen replication rates increase and intensify the immunological challenges on the host. This situation creates a synergistic effect through the simultaneous escalation of pathogen pressure and immune stress [363]. Furthermore, increased temperatures can accelerate the host's metabolic processes, which improves their immune response in the initial stages. Nevertheless, prolonged thermal stress may result in immune suppression, mainly when the pathogen load is also high. This occurrence is primarily attributed to climate change.

Pollutants such as heavy metals and organic pollutants are abiotic factors that can disrupt immune function by interfering with signalling pathways or inducing oxidative stress, diminishing the organism's ability to respond to biotic threats. Under specific circumstances, an antagonistic effect may occur. For example, certain pollutants can reduce pathogen viability, thereby reducing disease transmission and alleviating immune pressure on the host [[364], [365], [366]]. Salinity fluctuations can also affect immune function and pathogen dynamics. Increased salinity can lead to osmoregulatory stress, which may impair immune function. Conversely, this condition can also create an unfavourable environment for pathogens and decrease the overall biotic challenge. The connection among these factors is dependent on species and ecological context. In summary, the equilibrium between synergistic and antagonistic interactions results from the cumulative and context-dependent effects of environmental and biological stressors on the immune systems of aquatic organisms.

Adaptation and immunological plasticity

Immune plasticity refers to the ability of aquatic animals to utilise diverse immune strategies to adapt to extreme environments and fluctuating conditions. This plasticity enables dynamic modifications to immune function in reaction to environmental stressors, including temperature variations, salinity alterations, and pathogen presence. Changes in aquatic species subjected to pollution and temperature variations have been noted, which enhance their immune responses to environmental stressors [367,368]. In extreme environments, such as polar regions or deep-sea habitats, immune systems must adapt to low pathogen diversity while retaining the capacity to respond effectively to pathogenic threats [369]. Antarctic fish have adapted to freezing temperatures by enhancing the production of heat shock proteins, which support immune function during thermal stress [[162], [370]]. Deep-sea organisms possess distinct immune receptor proteins to identify and react to specific microbial threats in their environments [371].

Short-term acclimatisation is a vital mechanism through which aquatic animals enhance immune function temporarily in reaction to environmental changes. The process sometimes involves immune priming, equipping the organism for more significant challenges. Exposure to minor elevations in temperature or salinity promotes their immune defences. An upregulation in pro-inflammatory cytokines and immune-regulating molecules was evident in O. niloticus (Nile tilapia) after short-term exposure to elevated salinity, which enhanced its immune response [372,373]. In addition, organisms can experience metabolic reprogramming to reallocate energy resources to enhance immune functions in response to environmental stress. Studies have detected this process in zebrafish during temporary temperature elevations [374,375].

Epigenetic mechanisms also significantly contribute to immune plasticity in response to long-term environmental changes such as ocean warming or acidification. For instance, DNA methylation and histone modification enable organisms to rapidly modify gene expression in reaction to environmental challenges without changing the fundamental genetic code. Evolution has allowed epigenetic changes to be established within populations, manifested as adaptations to improve survival in extreme environments. In summary, aquatic animals depend on short-term acclimatisation mechanisms and long-term evolutionary adaptations to survive and thrive under extreme and fluctuating conditions. Adaptations are frequently driven by immune plasticity, supported by epigenetic modifications allowing swift and reversible reactions to environmental changes.

Implications for aquaculture and conservation

Immune responses to biotic and abiotic factors are essential for the health and survival of aquatic animals, significantly impacting aquaculture practices and the conservation of wild populations. In fish and shrimp farming, bacteria, viruses, and parasites are biotic factors that can significantly impair the immune systems of cultured species, leading to increased mortality rates and considerable economic losses. Vibrio species are known to cause diseases in shrimp, highlighting the importance of understanding pathogen-host dynamics for developing effective disease management strategies [376]. Additionally, abiotic factors, including environmental conditions like temperature, salinity, pH, and pollutant presence, significantly influence immune function. Variations in water temperature can intensify stress responses, leading to compromised immune function and heightened vulnerability to infectious diseases [377]. Therefore, aquaculture operations must identify and address these environmental stressors to ensure the optimal health of cultured species.

Various strategies can be implemented to improve immune health in aquaculture. The added benefit of probiotics has demonstrated the potential to enhance gut microbiota, improve digestion, and augment immune responses in aquatic animals [378]. Probiotics such as Lactobacillus and Bacillus can help prevent disease outbreaks in tilapia and shrimp by competing against harmful pathogens and enhancing their health [379]. Beta-glucans and mannan oligosaccharides are immune stimulants incorporated in the diets of cultured species to activate and improve the immune response and disease resistance [380]. Maintaining optimal environmental conditions is also crucial in enhancing the immune health of cultured organisms, which involves the consistent monitoring of water quality parameters, such as temperature, salinity, and oxygen level and prompt corrective actions when necessary. Biosecurity measures such as access control to farms and prevention of cross-contamination can significantly reduce the risk of disease outbreaks [[380], [381], [382]].

Environmental changes significantly threaten immune functions in wild populations, resulting in biodiversity decline. Climate change, pollution, habitat degradation, rising ocean temperatures and altered salinity levels negatively impact the immune systems of wild fish and invertebrates, increasing their susceptibility to diseases. Coral reef fish also become immunocompromised when exposed to higher temperatures, increasing their mortality rates during disease outbreaks [[383], [384], [385], [386]]. Furthermore, pollution from heavy metals and microplastics impaired immune functions in multiple species, including salmon, thus contributing to population declines [387,388].

These challenges highlight the necessity of immunological adjustment strategies to conserve endangered aquatic species. Immunocompromised populations in the wild may be more vulnerable and at risk of biodiversity losses. Prioritising habitat preservation and restoration can help maintain the immune health of wild aquatic species and survive environmental changes [389]. Understanding the complex interactions between immune responses and environmental factors is crucial for advancing aquaculture sustainability and strengthening conservation efforts for wild aquatic populations.

Future research directions

Climate change, habitat degradation, and rising pollution levels have contributed to the emergence of novel diseases in aquatic ecosystems. Increasing global temperatures modified the immune responses of coral reef fish, increasing their susceptibility to pathogens such as Vibrio spp. that thrive in warmer waters [390]. Coastal development and pollution are examples of habitat degradation that disrupt the ecosystem balance and offer an optimal environment for opportunistic pathogens [391]. Heavy metals and microplastics pollution also induce immunotoxicity in aquatic species that prevent them from responding effectively to infections. These challenges underscore the necessity for additional research to investigate the interactions between novel pathogens and extreme environmental conditions and their effects on aquatic immune systems. Comprehending these intricate dynamics is crucial for formulating effective management strategies to reduce the risks associated with emerging diseases and safeguard the health of wild and farmed aquatic species.

Genomics, proteomics, and immunologic advancements offer essential tools for improving our comprehension of aquatic immune responses. The integration of these technologies may facilitate the development of biomarkers that indicate immune health, offering insights into population resilience in varying environments. Genomic technologies help identify genetic markers linked to disease resistance and immune function in aquaculture, enabling selective breeding of resilient strains [392,393]. Proteomic analyses aid in the detection od specific proteins associated with immune responses, elucidating how aquatic organisms adapt to environmental stressors [393]. In addition, biosensors and non-invasive monitoring systems are promising innovations for monitoring immune health in wild and cultured species. Wearable biosensors can transform aquaculture management by facilitating real-time fish health assessments by observing physiological parameters indicative of immune status [394]. Utilizing these technological advancements enables researchers and aquaculturists to understand the complexities of aquatic immune systems and improve their resilience against emerging threats.

Conclusion

Biotic and abiotic factors interact and influence the immune responses of aquatic animals. Under environmental pressures and elevated pathogen loads, immune suppression may occur in various species. Pollution, temperature variations, and salinity changes also reduce the organism’s capacity to defend themselves against pathogens. As climate change continues to modify aquatic environments, understanding these interactions is critical for managing farmed and wild aquatic populations and providing optimal environments to improve their immune resilience. Therefore, it is recommended that future research investigate species-specific responses to environmental stressors and develop strategies to alleviate the impacts of pollution, temperature fluctuations, and pathogen pressure on the immune health of aquatic species in their respective ecosystems.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author

Funding statement

The primary source of funding for this research project was provided by the Ministry of Education Malaysia under the Fundamental Research Grant Scheme (FRGS) (FRGS/1/2022/STG03/UMK/03/1).

Ethics approval statement

Not applicable.

Patient consent statement

Not applicable.

Permission to reproduce material from other sources

Not applicable.

CRediT authorship contribution statement

Zulhisyam Abdul Kari: Writing – review & editing, Writing – original draft, Supervision.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.