Integrated transcriptomic and metabolomic analysis of the hepatopancreas in Crassostrea hongkongensis under mercury (Hg) stress

Against a backdrop of increasingly severe marine heavy-metal pollution, bioaccumulation now poses a grave threat to aquaculture species and sector sustainability. To investigate the response mechanisms of bivalve mollusks under heavy metal stress, Crassostrea hongkongensis were exposed to 0.506 mg/L Hg (96-h LC 50 ) in filtered seawater. The activities of antioxidant enzymes were subsequently measured at 0 h, 24 h, 48 h, 72 h, and 96 h post-exposure, while transcriptomic and metabolomic analyses were performed on hepatopancreas samples collected at designated time points. The results showed that the antioxidant enzyme responses, including SOD, CAT, and GSH-Px, were both time- and tissue-dependent. While activities in the adductor muscle, gills, and mantle peaked at 24 h before declining, the hepatopancreas showed significant suppression until 72 h, followed by partial recovery at 96 h, indicating the activation of tissue-specific repair mechanisms against prolonged oxidative stress. Transcriptome sequencing revealed 5383 DEGs enriched in the NF-κB and Lysosome pathways. Metabolomics analysis identified 297 and 181 unique DEMs in positive and negative ion modes, respectively, with significant enrichment in key metabolic pathways such as amino acid and pyruvate metabolism. Integrated analysis revealed co-enrichment of DEGs and DEMs across 119 pathways including Lysosome and Glutathione metabolism, which demonstrate C. hongkongensis counteracts Hg toxicity through coordinated activation of antioxidant, detoxification, and immune responses. This study reveals the comprehensive mechanisms by which C. hongkongensis adapts to Hg-induced stress, providing candidate biomarkers for early warning of coastal Hg pollution and laying a theoretical foundation for stress-resilient breeding in shellfish. • Hepatopancreas exhibits unique suppression-recovery antioxidant pattern under Hg stress in C. hongkongensis . • Integrated transcriptomic and metabolomic analysis reveals 5383 DEGs and 478 DEMs under Hg exposure. • Glutathione and cytochrome P450 pathways co-enriched, indicating coordinated detoxification response. • Hg exposure activates NF-κB and NOD-like receptor innate immune pathways in the oyster hepatopancreas.