Integrated transcriptomic and co-expression analyses reveal hypoxia-responsive patterns in the gills of Mytilus...

Hypoxia is a significant environmental stressor that negatively affects the growth, survival, and overall health of marine bivalves. This study aimed to investigate the physiological and molecular responses of Mytilus coruscus (thick-shell mussel) to hypoxic stress by integrating histological analysis, enzyme activity assays, whole-transcriptome sequencing, and Weighted Gene Co-expression Network Analysis (WGCNA) of gill tissues. The results revealed marked structural damage to gill filaments under prolonged hypoxia, including epithelial swelling, exfoliation, and lamellar fusion. Enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), exhibited distinct temporal fluctuations, with an initial decrease followed by partial recovery at later time points. WGCNA identified four gene co-expression modules associated with hypoxia exposure, and these modules were enriched in pathways related to metabolic regulation, stress response, and antioxidant defense. Transcriptome sequencing identified 56 differentially expressed miRNAs, 1393 mRNAs, 392 lncRNAs, and 21 circRNAs, and RT-qPCR validation confirmed the consistency of the expression trends of selected mRNAs. Functional enrichment analysis indicated that hypoxia-responsive coding and non-coding transcripts were associated with signaling pathways involved in stress response, energy metabolism, and antioxidant defense. Together, these findings support a transcriptome-based working model in which FOXO and HIF-1-related pathways may participate in hypoxia-associated metabolic and antioxidant adjustment in M. coruscus. These results provide candidate targets for future functional validation and may offer a basis for aquaculture management strategies aimed at improving stress resilience.