Growth-Linked, Tissue-Specific Antioxidant Reprogramming During Natural Zn/Cu Bioaccumulation in the Pacific Oyster Magallana gigas

Whether zinc (Zn) and copper (Cu) bioaccumulation in the Pacific oyster (Magallana gigas) reflects toxicological stress or is an incidental consequence of growth remains unclear. We cultured three commercial triploid M. gigas stocks for approximately one year, sampling gill and hepatopancreas at the start and end of this period, when Zn/Cu burden was naturally low and high, respectively. Pooled samples from both time points were profiled by whole-transcriptome sequencing, enzyme activity and oxidative damage assays, qPCR validation, and protein–protein interaction network analysis. Transcriptome-wide changes in both tissues tracked the culture period, but growth and Zn/Cu burden were too highly collinear (r = 0.92–0.98) to separate statistically. Critically, of the four metals measured (Zn, Cu, iron [Fe], and manganese [Mn]), only Zn and Cu increased with growth, whereas Fe and Mn did not, indicating metal-specific rather than generalized accumulation. Superoxide dismutase (SOD) activity and the transcript abundance of its copper/zinc isoform (Cu/Zn-SOD) increased with growth in both tissues, whereas catalase (CAT) activity was unchanged and glutathione peroxidase (GPX) activity rose only in gill. Malondialdehyde (MDA), a marker of oxidative damage, increased in both tissues. Gill mounted a broader response than hepatopancreas, including upregulation of KEAP1 alongside downregulation of detoxification, proteostasis, and ribosome-related genes. Stock-level qPCR further revealed stock-dependent regulation of antioxidant genes in hepatopancreas. Together, these results indicate that Zn/Cu bioaccumulation in M. gigas co-varies with growth in a metal-specific manner, consistent with cofactor demand for Cu/Zn-SOD. The accompanying oxidative and proteostatic changes therefore more plausibly reflect growth physiology than an independent pollutant signal.