Résumé
Pacific Oyster Mortality Syndrome (POMS) represents a major threat to the global Magallana gigas socio-ecosystem. This panzootic and polymicrobial disease, primarily caused by the virus OsHV-1, has led to substantial economic losses in the oyster aquaculture industry. Temperature, nutrition, and age strongly influence susceptibility to POMS, making it a multifactorial disease. Notably, oyster ageing confers resistance to POMS; however, the molecular mechanisms driving this age-dependent resistance remain to be characterised. To address this, offspring from four bi-parental families (H2D, F14R, F11N and F14V) were exposed to OsHV-1 μVar at 4, 16, and 28 months old. Survival rates showed family-specific differences and increased linearly with age. For both H2D and F14R families, six individuals of each age were analysed (basal conditions) using multi-omics integrating DNA methylation, transcriptome, and metabolite analysis. Our findings revealed for both families, common and family-specific positive and negative regulations with ageing in several key processes, such as cellular development, metabolic functions, signal transduction, and defence responses to viruses at the epigenetic and transcriptomic layers. Interestingly, we observed increased DNA methylation levels in the gene body region of 19 genes involved in immune processes (e.g., TIR domain-containing proteins and TNF receptor-associated factor). We observed in parallel an underexpression of several genes involved in the MyD-88-dependent immune pathway. Additionally, we identified age-associated metabolic changes, such as the accumulation of TCA cycle compounds in older oysters, illustrating a metabolic shift favouring energy utilization for immune defence and cellular repair. Integrating epigenetic, transcriptomic and metabolic data, we highlighted the transition from a permissive to a non-permissive state, underpinning age-dependent acquisition of resistance. By identifying age-specific biomarkers and epigenetic signatures linked to POMS disease resistance, this study lays the foundation for innovative strategies in disease management and breeding programs, ultimately enhancing the resilience of Pacific oysters to POMS.