Coasts and their marine biota are exposed to major environmental heterogeneity as a consequence of natural drivers and anthropogenic stressors. Here, individuals of the mussel Perumytilus purpuratus from two different geographical populations exposed to contrasting environmental conditions (i.e. estuarine versus open coastal conditions) were used in a reciprocal transplant and a laboratory experiment with the aim of determining the grade of of local adaptation to their native sites, as well as their sensibility to ocean acidification. After characterizing environmentally the coastal habitats, a set of life-history traits and a phenotypic plasticity index were determined for both mussel populations. From the reciprocal transplant experiment, we observed that mussels originally coming from the estuarine habitat exhibited a distinctive performance pattern usually associated with physiological stress (i.e. higher metabolic rates, lower calcification and growth rates) leading to important physiological trade-offs and higher levels of phenotypic plasticity. Alternatively, mussels originating from the open coastal site showed lower physiological phenotypic plasticity suggesting a high grade of local adaptation to their habitat. In addition, both populations responded very similarly to lower pH conditions (i.e. increased metabolic rates with no important effects on growth and calcification, and lower physiological phenotypic plasticity). The study results indicated that overall estuarine conditions more than isolated pH changes would be modulating the performance and the level of phenotypic plasticity of the two P. purpuratus geographical populations studied. Our study also emphasizes the necessity of characterizing phenotypic plasticity under multiple-driver environments to cast more accurate predictions about the susceptibility of marine biota to future climate stressors such as ocean acidification.