Immune homeostasis as the missing link between systemic fungicide exposure and pathogen susceptibility in aquatic animals.

Systemic fungicides are widely used in modern agriculture and are increasingly detected in aquatic environments, raising concerns about their potential effects on non-target aquatic organisms. Unlike conventional toxicological studies that primarily focus on acute toxicity, oxidative stress, or organ damage, emerging evidence suggests that sublethal fungicide exposure may also disturb immune regulation and compromise host defense. This review systematically summarizes the environmental occurrence and biological effects of major systemic fungicides, including triazoles, strobilurins, benzimidazoles, and other systemic fungicides, in aquatic animals. Available evidence indicates that fungicide exposure can induce developmental and organ-specific toxicity, disrupt barrier integrity, alter immune-related responses, and interfere with cellular processes involved in immune regulation, including oxidative balance, mitochondrial function, endocrine signaling, and energy metabolism. Importantly, these effects differ in their relevance to host immunity: general physiological toxicity and changes in individual immune biomarkers should not be considered equivalent to functional immune impairment. Recent studies provide direct evidence that azoxystrobin and trifloxystrobin can impair antiviral defense and increase susceptibility to rhabdovirus infection in fish, whereas comparable pathogen-challenge evidence for other fungicides, pathogens, and aquatic animal taxa remains limited. Based on these findings, we propose immune homeostasis as a conceptual link between systemic fungicide exposure and altered host defense, and highlight the need to integrate environmentally realistic exposure, functional immune endpoints, mechanistic validation, and pathogen-challenge models into aquatic immunotoxicology. This immune homeostasis-centered perspective may improve the assessment of disease-related risks associated with chronic fungicide exposure and provide a basis for understanding how environmental chemical stress contributes to disease susceptibility in aquatic animals.