The black mussel Mytilus galloprovincialis is an ideal organism for studying adaptation as it inhabits highly variable environments. We examined its acclimation to long-term osmostress using time-series experimentation and RNA-seq based transcriptomics approaches. In our results, osmotic homeostasis was enhanced by alterations of membrane permeability and nitrogen metabolism. Cholinergic ciliary stimulation and calcium signaling were involved in the response. Genes encoding protein turnover, carbohydrate metabolism/catabolism, nucleotide metabolism, arachidonic acid metabolism, aerobic and anaerobic energy metabolisms, and apoptosis were all inversely regulated with salinity. In addition, we observed two novel metabolic regulations; first, the involvement of anaerobic to aerobic metabolism as previously suggested to exist in bivalves, and second, the regulation of PEPCK with OXPHOS and glycolysis genes. These two regulations are significant due to their similarities to the metabolic regulations seen in cancer cells. Although there are many types/causes of cancer, there are common adaptations that support its survival, including the aforementioned metabolic regulations and apoptosis suppression. In parallel to these regulations, we observed p53 and p63 originated apoptosis with the participation of TP53 apoptosis effector (PERP), TLRs, and TNFSF14. Understanding the genes, pathways and modifications that trigger the mechanism that sets off cell death in this context can be promising for cancer and in developing therapeutic and protective products such as vaccines.