We present a large set of spectral lines detected in the $40$ central region of the starburst galaxy NGC 253. Observations were obtained with the three instruments SPIRE, PACS and HIFI on board the Herschel Space Observatory, upGREAT on board of the SOFIA airborne observatory, and the ground based APEX telescope. Combining the spectral and photometry products of SPIRE and PACS we model the dust continuum Spectral Energy Distribution (SED) and the most complete $^{12}$CO Line SED reported so far toward the nuclear region of NGC 253. Properties and excitation of the molecular gas were derived from a three-component non-LTE radiative transfer model, using the SPIRE $^{13}$CO lines and ground based observations of the lower-$J$ $^{13}$CO and HCN lines, to constrain the model parameters. Three dust temperatures were identified from the continuum emission, and three components are needed to fit the full CO LSED. Only the third CO component (fitting mostly the HCN and PACS $^{12}$CO lines) is consistent with a shock/mechanical heating scenario. A hot core chemistry is also argued as a plausible scenario to explain the high-$J$ $^{12}$CO lines detected with PACS. The effect of enhanced cosmic ray ionization rates, however, cannot be ruled out, and is expected to play a significant role in the diffuse and dense gas chemistry. This is supported by the detection of ionic species like OH$^+$ and H$_2$O$^+$, as well as the enhanced fluxes of the OH lines with respect to those of H$_2$O lines detected in both PACS and SPIRE spectrum.
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