show Abstracthide AbstractOcean acidification is increasing due to anthropogenic CO2 emissions, and poses a threat to marine species and communities worldwide. To better predict the effects of acidification on species’ health and persistence an understanding is needed of (1) mechanisms underlying developmental and physiological tolerance, and (2) an assessment of the potential for rapid evolutionary adaptation. This is especially challenging in non-model species where targeted assays of metabolism and stress physiology may not be available or economical enough to use for large-scale assessments of genetic constraints. We used mRNA sequencing and a quantitative genetics breeding design to study mechanisms underlying genetic variability and tolerance of the predicted 0.4 unit decline seawater pH by the year 2100 in larvae the sea urchin Strongylocentrotus droebachiensis. We used a gene ontology-based approach to integrate expression profiles into indirect measures of cellular and biochemical traits underlying variation in larval performance (i.e., growth rates or mortality). Molecular responses to OA were complex, involving changes to growth rates, cell division, metabolism, and immune activities. Surprisingly, the magnitude of pH effects on molecular traits effects tended to be small relative to variation caused by segregating functional genetic variation in this species. We discuss how the application of transcriptomics and quantitative genetics approaches across diverse species can enrich our understanding of the biological impacts of climate change.