The bivalve Arctica islandica is extremely long lived (>400 years) and can tolerate long periods of hypoxia and anoxia. European populations differ in maximum life spans from 40 years in the Baltic to >400 years around Iceland. Characteristic behavior In their natural environment and under laboratory conditions,of A. islandica performs involves phases of metabolic rate depression (MRD) during which the animals burry into the sediment for several days and which suggested possibly supporting the long life span of some populations. The animals burrow into the sediment for some days an In the buried state d lower shelshell water oxygen concentrations to hypoxic andreaches even anoxic levels. In the present study wWe investigated gene regulation in individuals A. islandica fromof the a longer- lived (MLSP 150years) German Bight population and the a shorter- lived Baltic Sea population, experimentally exposed to different oxygen levels. A new A. islandica transcriptome enabled the identification of genes important during hypoxia/anoxia events and, more generally, gene mining for putative stress response and (anti-) aging genes. Exposed to low oxygen (0 and 2 kPa) conditions, German Bight individuals generally suppress gene transcription, whereas Baltic Sea bivalves enhanced gene transcription under anoxic incubation (0 kPa), and, further, decreased these transcription levels again during 6h of re-oxygenation. Hypoxic and anoxic exposure and subsequent re-oxygenation in Baltic Sea animals did not lead to increased protein oxidation or induction of apoptosis, emphasizing considerable hypoxia/re-oxygenation tolerance of in this species. The data suggest that the energy saving effect of MRD may not be an attribute of Baltic Sea A. islandica chronically exposed to high environmental variability of oxygenation and also temperature and salinity. Contrary, higher physiological flexibility and stress hardening may predispose these animals to perform a pronounced stress response at the expense of life span.