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The topographic history of an orogen, a key element to study the interactions of the climate and tectonic conditions that drove it, can be reconstructed by inverting the sedimentary record of its adjacent basins. Previous tectono-stratigraphic studies, including flexural models, and sparse stable oxygen and carbon isotope data from the South-Pyrenean foreland basin suggest a major topographic rise occurred in the late Paleocene-early Eocene. To further test this hypothesis, we present a stack of 658 stable isotope measurements on whole-rock marine carbonate mudstone from a 4800-m-thick composite sedimentary succession which provides a 12 Ma continuous record of environmental conditions during the early to middle Eocene (54 to 42 Ma). From the base of this record (at 54 Ma), oxygen isotopes (δ18O values) show a faster decrease rate than the coeval global negative excursion associated with the Early Eocene Climatic Optimum (EECO). This local alteration of the global δ18O signal indicates that topographic growth during this period, associated with significant tectonic activity, perturbed the oxygen isotopic composition of foreland waters. Thus, our data suggest that significant topographic uplift of the Pyrenean orogen started from at least 54 Ma and continued until ca. 49 Ma, reaching the maximum elevations of 2000 ± 500 m in this phase from previous isotope and flexural studies. In addition, our record shows that the long-term carbon stable isotope composition during this period remained relatively stable with no similarity to the global bell-shaped long-term trend of the EECO. This is consistent with the restricted physiography of the South-Pyrenean foreland basin, mainly influenced by local sedimentary and water inputs. Overall, the Pyrenean topographic growth from the late Cretaceous to the Miocene displays several growth stages that seem to be primarily determined by episodes of increased rate of tectonic plate convergence. The duration of these growth stages (several millions of years) is a possible documentation of the response time of mountain ranges to tectonic perturbations. The results of this work, therefore, demonstrate that stable isotope measurements on whole-rock sediments in foreland basins can provide key information for tectono-climatic and topographic reconstructions of mountain ranges. [ABSTRACT FROM AUTHOR]