Aquaculture-relevant florfenicol exposure causes hepatopancreatic bioaccumulation and metabolic-immune toxicity in the mud crab Scylla paramamosain.

The overuse of the broad-spectrum antibiotic florfenicol (FF) and its residues in coastal benthic environments pose toxicological risks to marine crustaceans. As an economically important benthic species, the mud crab is vulnerable to FF pollution stress, yet its toxicological responses and underlying mechanisms remain unclear. Therefore, this study investigated the physiological, biochemical, and transcriptomic responses of the mud crab hepatopancreas following FF exposure. Healthy mud crabs were assigned to one control group and three FF exposure groups (5, 50, and 500 μg/L) and exposed for 10 days. The results demonstrated that FF accumulated in the hepatopancreas in a concentration-dependent manner, significantly reduced the weight gain rate and hepatosomatic index, and induced marked histopathological alterations. Furthermore, FF stress significantly elevated MDA content, disrupted the homeostasis of antioxidant and detoxification systems (including SOD, CAT, GST, GSH, and T-AOC), and induced oxidative stress. Transcriptomic analysis and gene set enrichment analysis (GSEA) showed that FF impaired lipid metabolism mainly by suppressing PPAR signaling and inhibiting fatty acid synthesis and degradation. FF exposure was also associated with persistent downregulation of melanogenesis-related pathways, suggesting potential impairment of innate immune-related functions. These alterations likely contributed to growth inhibition in mud crabs under FF stress. Weighted gene co-expression network analysis (WGCNA) combined with protein-protein interaction (PPI) analysis identified HSPA8 and phc-2 as candidate hub genes potentially associated with compensatory detoxification and epigenetic growth restriction, respectively. These findings elucidate the molecular regulatory networks underlying FF-induced hepatopancreatic damage, providing useful evidence for the environmental risk assessment and toxicological evaluation of antibiotic residues in mud crab aquaculture.