The effect of structural imperfections as well as oxygen impurities on the quantum conductance of poly(3-hexylthiophene) is calculated from first principles by solving the scattering problem for molecular structures obtained within density functional theory It is shown that the conductivity of molecular crystals perpendicular to the polymer chains depends strongly on the stacking geometry and is roughly described within the Wentzel-Kramers-Brillouin approximation Furthermore it is found that local relaxation for twisted or bent 6320 polymer chains efficiently restores the conductance that drops 13 to substantially for sharp kinks with curvature radii smaller than 17 angstrom and rotations in excess of similar to 60 degrees In contrast isomer defects in the coupling along the chain direction are of minor importance for the intrachain transmission Also oxidation of the side chains as well as molecular sulfur barely changes the coherent transport properties, whereas oxidation of thiophene group carbon atoms drastically reduces the conductance