Survival is highly dependent on an organism’s resilience in stress conditions. Model organisms such as C. elegans have been pivotal in successfully identifying genes that increase stress resilience, broadening our understanding of how organisms protect themselves from the severe damage that stress can cause on a cellular level. Despite the seemingly positive effects of mutations in these stress resistance genes, they have not evolved in nature, showing a discrepancy in efforts to understand the natural genetic basis of resilience. Using time-course experiments in combination with global transcriptomics, we show that the extent to which the transcriptome adapts during severe stress encompasses a wide-ranging shift in expression dynamics of thousands of genes. This result emphasises the high complexity of the immediate response to stress. Expanding on these findings, we show that recovery is not a simple continuation or reversal of the stress response, but also involves a distinct set of genes with unique expression dynamics. Furthermore, the transcriptional state during recovery is a higher predictor of resilience in natural populations than the initial stress response. Our findings argue that, to fully understand the genetic basis of resilience, recovery requires increased attention as a distinct process contributing to resilience.
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