Co-exposure to microplastics and bisphenol A increases viral susceptibility in largemouth bass (Micropterus salmoides) via oxidative stress

Microplastics (MPs) and bisphenol A (BPA) frequently co-occur in freshwater ecosystems, yet their combined impacts on host-pathogen interactions remain poorly understood. Here, we exposed juvenile largemouth bass (Micropterus salmoides) to environmentally relevant concentrations of MPs, BPA, and their mixture. Co-exposure markedly inhibited NRF2-mediated antioxidant signaling, leading to downregulation of antioxidant enzymes (SOD1, CAT, GPx), elevated hepatic reactive oxygen species and malondialdehyde, and depletion of ATP. These redox disturbances were accompanied by mitochondrial damage, increased expression of pro-apoptotic genes (Bax, Caspase-3), and accumulation of TUNEL-positive nuclei, indicative of apoptosis. Strikingly, only co-exposed fish exhibited enhanced replication of nervous necrosis virus (NNV), a response absent under single exposures. Our findings demonstrate that MPs and BPA act synergistically to disrupt redox homeostasis and compromise antiviral defense, thereby heightening viral susceptibility in a freshwater aquaculture species. This study highlights the overlooked infection risks posed by pollutant mixtures and emphasizes the need to incorporate mixture toxicity into freshwater ecotoxicological risk assessments.