Dose-dependent effects of strontium on the calcification physiology of Ruditapes philippinarum larvae

Strontium (Sr) is a calcium-analog that can accumulate in coastal environments from natural and anthropogenic sources, posing emerging risks to ecosystems and human health. By readily entering calcium-based biomineralization pathways, Sr can disrupt the calcification physiology of marine calcifiers, yet the dose-dependent effects remain poorly constrained. Here, we assessed the impact of Sr across a large concentration gradient (0-80 mg L^-1) on the early larval development of the Manila clam (Ruditapes philippinarum). Complete absence of Sr prevented initiation of prodissoconch I (PD I) formation, whereas normal shell building was restricted to a narrow Sr concentration window (4-16 mg L^-1), with optimal performance at 8 mg L^-1. In contrast, elevated Sr concentrations (>24 mg L^-1) caused pronounced developmental abnormalities and reduced shell growth. Shell geochemical analyses revealed a linear increase in the Sr/Ca molar ratio with environmental Sr, indicating direct incorporation into the shell mineral phase. Transcriptomic analyses showed minimal differences between Sr-deficient and optimal conditions, suggesting a physicochemical role in initiating shell calcification, whereas excessive Sr exposure triggered strong transcriptional responses related to energy metabolism, oxidative stress and cell death. Our findings define a narrow threshold between seawater essential and toxic Sr concentrations and provide a critical framework for environmental hazard assessment in bivalves and ecosystems they support.