The cave systems of the Neretva River basin in the Dinaric Karst are home to Congeria kusceri, one of the very few known examples of stygobiotic bivalve mollusks, which displays several unique life history traits and adaptations that allowed its adaptation to the subterranean environment. This endemic species is undergoing rapid decline, most likely linked with habitat degradation, which might seriously threaten its survival in the next few decades. Unfortunately, the urgent need for effective conservation efforts is hampered by the lack of effective regulations aimed at preserving remnant populations as well as by our limited knowledge of the biology of this species. Although the precise factors underlying the disappearance of C. kusceri from its type locations are not entirely clear, the alteration of seasonal changes in water temperatures and alkalinity is most likely involved, as these are the main drivers of shell growth, spawning, and the onset and progression of the new gametogenic cycle. While these aspects have so far only been studied using morphological and physiological observations, future conservation efforts would certainly benefit from an integrated multidisciplinary approach. Here, using RNA-sequencing, we provide an overview of the modulation of gene expression recorded in five key tissues (the mantle, gonads, gills, adductor muscle, and digestive gland) between early June and late September. We highlight the presence of markedly tissue-specific responses, with the most dramatic changes affecting the gonads, mantle, and gills. We further identified a drastic switch in the use of energy budgets between the two periods, with evidence of ongoing shell growth and high metabolic activity in the mantle and gills at the early time point, followed by a massive redirection of all available energy to the gonads for the generation of new gamete primordia in early autumn.